Magnetoreceptive CRY/MagR complexes: linking circadian redox signalling to protein aggregation in Alzheimer’s and Parkinson’s disease: Review

Mozhgan Alipour; Behnam Hajipour-Verdom; Faria Ashrafi; Sara Rahmati Roodsari; Shabnam Nohesara; Alireza Zali; Farzad Ashrafi

doi:10.5599/admet.3366

Authors

Mozhgan Alipour Functional Neurosurgery Research Center, Research Institute of Functional Neurosurgery, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0002-3894-6331
Behnam Hajipour-Verdom Department of Integrative Oncology, Breast Cancer Research Center, Motamed Cancer Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, 1517964311, Iran https://orcid.org/0000-0002-9799-6849
Faria Ashrafi Department of Biology, University of Massachusetts Amherst, Amherst, MA 01003, USA https://orcid.org/0009-0006-3898-9629
Sara Rahmati Roodsari Functional Neurosurgery Research Center, Research Institute of Functional Neurosurgery, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0003-1977-9440
Shabnam Nohesara Department of Medicine (Biomedical Genetics), Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA https://orcid.org/0000-0003-4944-7033
Alireza Zali Functional Neurosurgery Research Center, Research Institute of Functional Neurosurgery, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0002-2298-2290
Farzad Ashrafi Functional Neurosurgery Research Center, Research Institute of Functional Neurosurgery, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0002-5959-5462

DOI:

https://doi.org/10.5599/admet.3366

Keywords:

Cryptochrome, magnetoreceptor, oxidative stress, circadian rhythms

Abstract

Background and purpose: Neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) pose an escalating challenge to neuroscience, as disease-modifying therapies remain elusive despite substantial advances in molecular and cellular understanding. These disorders share convergent pathological features, including protein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, impaired proteostasis, and disruption of circadian regulation. Identifying integrative frameworks that connect these processes is therefore essential for advancing conceptual models of neurodegeneration. This review examines magneto-proteins, with a particular focus on CRY/MagR-based magnetoreceptor complexes, as emerging biological systems that may intersect with key molecular pathways implicated in AD and PD. Experimental approach: We synthesized literature from neuroscience, biophysics, and circadian biology to evaluate the potential relevance of magnetoreceptor mechanisms to AD and PD pathology. We first summarized the core neuropathological mechanisms underlying both diseases, including amyloid-β and tau pathology in AD and α-synuclein aggregation and dopaminergic vulnerability in PD. We then outlined the biophysical foundations of magneto-protein function, emphasizing cryptochrome-mediated radical pair mechanisms, iron-sulfur cluster-dependent magnetic sensitivity, and their established roles in redox signaling and circadian biology. Key results: Accumulating experimental evidence from cellular and animal models suggests that CRY/MagR-associated pathways can modulate oxidative stress, mitochondrial bioenergetics, protein aggregation dynamics, autophagic processes, and circadian control of neuronal metabolism. These processes closely overlap with molecular determinants of neuronal vulnerability in AD and PD. However, direct validation in mammalian and human systems remains limited and controversial, representing a critical knowledge gap. Conclusion: The mechanistic convergence between magnetoreceptor biology and neurodegenerative pathology warrants critical evaluation but remains largely speculative in humans. By integrating findings across disciplines, this review positions CRY/MagR-based magneto-proteins as a conceptual platform for exploring how magnetic field-responsive molecular systems may inform our understanding of neurodegenerative disease mechanisms, while emphasizing the need for rigorous mammalian validation.

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References

[1] E. Nichols, J.D. Steinmetz, S.E. Vollset, K. Fukutaki, J. Chalek, F. Abd-Allah, A. Abdoli, A. Abualhasan, E. Abu-Gharbieh, T.T. Akram. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. The Lancet Public Health 7 (2022) e105-e125. https://doi.org/10.1016/S2468-2667(21)00249-8 DOI: https://doi.org/10.1002/alz.051496

[2] E.R. Dorsey, A. Elbaz, E. Nichols, N. Abbasi, F. Abd-Allah, A. Abdelalim, J.C. Adsuar, M.G. Ansha, C. Brayne, J.-Y.J. Choi. Global, regional, and national burden of Parkinson's disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology 17 (2018) 939-953. https://doi.org/10.1016/S1474-4422(18)30295-3 DOI: https://doi.org/10.1016/S1474-4422(18)30295-3

[3] World Health Organization. Global status report on the public health response to dementia. World Health Organization, Geneva, Switzerland, 2021. https://www.who.int/publications/i/item/9789240033245 (Accessed February 15, 2026).

[4] W. Yang, J.L. Hamilton, C. Kopil, J.C. Beck, C.M. Tanner, R.L. Albin, E. Ray Dorsey, N. Dahodwala, I. Cintina, P. Hogan. Current and projected future economic burden of Parkinson’s disease in the US. npj Parkinson's Disease 6 (2020) 15. https://doi.org/10.1038/s41531-020-0117-1 DOI: https://doi.org/10.1038/s41531-020-0117-1

[5] M. Edwards, R. Corkill. Disease-modifying treatments in Alzheimer’s disease. Journal of Neurology 270 (2023) 2342-2344. https://doi.org/10.1007/s00415-023-11602-8 DOI: https://doi.org/10.1007/s00415-023-11602-8

[6] A. Lenka, J. Jankovic. How should future clinical trials be designed in the search for disease-modifying therapies for Parkinson’s disease? Expert Review of Neurotherapeutics 23 (2023) 107-122. https://doi.org/10.1080/14737175.2023.2177535 DOI: https://doi.org/10.1080/14737175.2023.2177535

[7] M.A. Wheeler, C.J. Smith, M. Ottolini, B.S. Barker, A.M. Purohit, R.M. Grippo, R.P. Gaykema, A.J. Spano, M.P. Beenhakker, S. Kucenas. Genetically targeted magnetic control of the nervous system. Nature Neuroscience 19 (2016) 756-761. https://doi.org/10.1038/nn.4265 DOI: https://doi.org/10.1038/nn.4265

[8] X. Long, J. Ye, D. Zhao, S.-J. Zhang. Magnetogenetics: remote non-invasive magnetic activation of neuronal activity with a magnetoreceptor. Science Bulletin 60 (2015) 2107-2119. https://doi.org/10.1007/s11434-015-0902-0 DOI: https://doi.org/10.1007/s11434-015-0902-0

[9] S. Safiri, A. Ghaffari Jolfayi, A. Fazlollahi, S. Morsali, A. Sarkesh, A. Daei Sorkhabi, B. Golabi, R. Aletaha, K. Motlagh Asghari, S. Hamidi. Alzheimer's disease: a comprehensive review of epidemiology, risk factors, symptoms diagnosis, management, caregiving, advanced treatments and associated challenges. Frontiers in Medicine 11 (2024) 1474043. https://doi.org/10.3389/fmed.2024.1474043 DOI: https://doi.org/10.3389/fmed.2024.1474043

[10] Q. Zheng, X. Wang. Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy. Protein & Cell 16 (2025) 83-120. https://doi.org/10.1093/procel/pwae026 DOI: https://doi.org/10.1093/procel/pwae026

[11] J.M. Long, D.M. Holtzman. Alzheimer disease: an update on pathobiology and treatment strategies. Cell 179 (2019) 312-339. https://doi.org/10.1016/j.cell.2019.09.001 DOI: https://doi.org/10.1016/j.cell.2019.09.001

[12] M.A. DeTure, D.W. Dickson. The neuropathological diagnosis of Alzheimer’s disease. Molecular Neurodegeneration 14 (2019) 32. https://doi.org/10.1186/s13024-019-0333-5 DOI: https://doi.org/10.1186/s13024-019-0333-5

[13] U.C. Müller, T. Deller, M. Korte. Not just amyloid: physiological functions of the amyloid precursor protein family. Nature Reviews Neuroscience 18 (2017) 281-298. https://doi.org/10.1038/nrn.2017.29 DOI: https://doi.org/10.1038/nrn.2017.29

[14] R.J. O'brien, P.C. Wong. Amyloid precursor protein processing and Alzheimer's disease. Annual Review of Neuroscience 34 (2011) 185-204. https://doi.org/10.1146/annurev-neuro-061010-113613 DOI: https://doi.org/10.1146/annurev-neuro-061010-113613

[15] D.D.-L. Chau, L.L.-H. Ng, Y. Zhai, K.-F. Lau. Amyloid precursor protein and its interacting proteins in neurodevelopment. Biochemical Society Transactions 51 (2023) 1647-1659. https://doi.org/10.1042/BST20221527 DOI: https://doi.org/10.1042/BST20221527

[16] M. Chen. The maze of APP processing in Alzheimer’s disease: where did we go wrong in reasoning? Frontiers in Cellular Neuroscience 9 (2015) 186. https://doi.org/10.3389/fncel.2015.00186 DOI: https://doi.org/10.3389/fncel.2015.00186

[17] A. Peric, W. Annaert. Early etiology of Alzheimer’s disease: tipping the balance toward autophagy or endosomal dysfunction? Acta Neuropathologica 129 (2015) 363-381. https://doi.org/10.1007/s00401-014-1379-7 DOI: https://doi.org/10.1007/s00401-014-1379-7

[18] U.C. Müller, H. Zheng. Physiological functions of APP family proteins. Cold Spring Harbor Perspectives in Medicine 2 (2012) a006288. https://doi.org/10.1101/cshperspect.a006288 DOI: https://doi.org/10.1101/cshperspect.a006288

[19] H. Zhang, Q. Ma, Y.w. Zhang, H. Xu. Proteolytic processing of Alzheimer’s β‐amyloid precursor protein. Journal of Neurochemistry 120 (2012) 9-21. https://doi.org/10.1111/j.1471-4159.2011.07519.x DOI: https://doi.org/10.1111/j.1471-4159.2011.07519.x

[20] R. Harrison, P. Sharpe, Y. Singh, D. Fairlie. Amyloid peptides and proteins in review. Reviews of Physiology, Biochemistry and Pharmacology 159 (2007) 1-77. https://doi.org/10.1007/112_2007_0701 DOI: https://doi.org/10.1007/112_2007_0701

[21] Y.J. Chang, Y.R. Chen. The coexistence of an equal amount of Alzheimer's amyloid‐β 40 and 42 forms structurally stable and toxic oligomers through a distinct pathway. The FEBS Journal 281 (2014) 2674-2687. https://doi.org/10.1111/febs.12813 DOI: https://doi.org/10.1111/febs.12813

[22] L.A. Rukmangadachar, P.C. Bollu. Amyloid beta peptide, In StatPearls, StatPearls Publishing, Treasure Island (FL). 2026. https://europepmc.org/article/NBK/nbk459119

[23] Y. Xiao, M. Zhang, N. Lu. Fluorescent Fingerprint Identification of Protein Structural Changes and Disease-Specific Amyloid Beta Aggregates Based on a Single-Nanozyme Sensor Array. Analytical Chemistry 97 (2025) 4978-4986. https://doi.org/10.1021/acs.analchem.4c05508 DOI: https://doi.org/10.1021/acs.analchem.4c05508

[24] S. Bagheri, L. Saso. Biophysical insights into the molecular mechanisms of beta amyloid aggregation and its toxic effects in Alzheimer's disease. Frontiers in Molecular Biosciences 12 (2025) 1704653. https://doi.org/10.3389/fmolb.2025.1704653 DOI: https://doi.org/10.3389/fmolb.2025.1704653

[25] W. Puławski, A. Koliński, M. Koliński. Multiscale modeling of protofilament structures: A case study on insulin amyloid aggregates. International Journal of Biological Macromolecules 285 (2025) 138382. https://doi.org/10.1016/j.ijbiomac.2024.138382 DOI: https://doi.org/10.1016/j.ijbiomac.2024.138382

[26] K. Khodayari, M. Alipour, I. Rad, H. Ramshini, P. Abdolmaleki. Inhibition potential evaluation of two synthetic bis-indole compounds on amyloid fibrillation: A molecular simulation study. Journal of Biomolecular Structure and Dynamics 40 (2022) 4051-4061. https://doi.org/10.1080/07391102.2020.1852962 DOI: https://doi.org/10.1080/07391102.2020.1852962

[27] K.B. Varshavskaya, I.Y. Petrushanko, V.A. Mitkevich, E.P. Barykin, A.A. Makarov. Post-translational modifications of beta-amyloid alter its transport in the blood-brain barrier in vitro model. Frontiers in Molecular Neuroscience 17 (2024) 1362581. https://doi.org/10.20944/preprints202312.1326.v1 DOI: https://doi.org/10.3389/fnmol.2024.1362581

[28] H. Hampel, J. Hardy, K. Blennow, C. Chen, G. Perry, S.H. Kim, V.L. Villemagne, P. Aisen, M. Vendruscolo, T. Iwatsubo. The amyloid-β pathway in Alzheimer’s disease. Molecular Psychiatry 26 (2021) 5481-5503. https://doi.org/10.1038/s41380-021-01249-0 DOI: https://doi.org/10.1038/s41380-021-01249-0

[29] M. Tolar, J. Hey, A. Power, S. Abushakra. Neurotoxic soluble amyloid oligomers drive Alzheimer’s pathogenesis and represent a clinically validated target for slowing disease progression. International Journal of Molecular Sciences 22 (2021) 6355. https://doi.org/10.3390/ijms22126355 DOI: https://doi.org/10.3390/ijms22126355

[30] M.S. Rafii, Z. Schlachetzki, I. Barroeta, E. Head, J. Fortea, B.M. Ances. Down syndrome and Alzheimer's disease: insights into biomarkers, clinical symptoms, and pathology. The Lancet Neurology 24 (2025) 753-762. https://doi.org/10.1016/s1474-4422(25)00237-6 DOI: https://doi.org/10.1016/S1474-4422(25)00237-6

[31] H. Zetterberg, K. Blennow. Moving fluid biomarkers for Alzheimer’s disease from research tools to routine clinical diagnostics. Molecular Neurodegeneration 16 (2021) 10. https://doi.org/10.1186/s13024-021-00430-x DOI: https://doi.org/10.1186/s13024-021-00430-x

[32] A. Azargoonjahromi, H. Nasiri, A.s.D.N. Initiative. CSF Amyloid-β42 associates with neuropsychiatric and cognitive outcomes via cerebral glucose metabolism. Molecular Brain 18 (2025) 55. https://doi.org/10.1186/s13041-025-01229-3 DOI: https://doi.org/10.1186/s13041-025-01229-3

[33] S.K. Saxena, S. Ansari, V.K. Maurya, S. Kumar, D. Sharma, H.S. Malhotra, S. Tiwari, C. Srivastava, J.T. Paweska, A.S. Abdel-Moneim. Neprilysin-mediated amyloid beta clearance and its therapeutic implications in neurodegenerative disorders. ACS Pharmacology & Translational Science 7 (2024) 3645-3657. https://doi.org/10.1021/acsptsci.4c00400 DOI: https://doi.org/10.1021/acsptsci.4c00400

[34] J. Chen, P. Xiang, A. Duro-Castano, H. Cai, B. Guo, X. Liu, Y. Yu, S. Lui, K. Luo, B. Ke. Rapid amyloid-β cle¬arance and cognitive recovery through multivalent modulation of blood–brain barrier transport. Signal Transduction and Targeted Therapy 10 (2025) 331. https://doi.org/10.1038/s41392-025-02426-1 DOI: https://doi.org/10.1038/s41392-025-02426-1

[35] L. Huang, M. Liu, Z. Li, B. Li, J. Wang, K. Zhang. Systematic review of amyloid-beta clearance proteins from the brain to the periphery: implications for Alzheimer’s disease diagnosis and therapeutic targets. Neural Regeneration Research 20 (2025) 3574-3590. https://doi.org/10.4103/nrr.nrr-d-24-00865 DOI: https://doi.org/10.4103/NRR.NRR-D-24-00865

[36] M.G. Iadanza, M.P. Jackson, E.W. Hewitt, N.A. Ranson, S.E. Radford. A new era for understanding amyloid structures and disease. Nature Reviews Molecular Cell Biology 19 (2018) 755-773. https://doi.org/10.1038/s41580-018-0060-8 DOI: https://doi.org/10.1038/s41580-018-0060-8

[37] I.A. Pereira, N.S. Rosa, R.R.N.R.d. Nascimento, E.A.M. Freire, F.d.S. Neves, B.E.R.G. Bica, F.A.G. Pinheiro, S.F. Perazzio, R.A. Cordeiro, H.A.M. Giardini. Uncovering the knowledge about systemic amyloidosis relevant to the rheumatologists. Advances in Rheumatology 64 (2024) 71. https://doi.org/10.1186/s42358-024-00399-3 DOI: https://doi.org/10.1186/s42358-024-00399-3

[38] J. Zhang, Y. Zhang, J. Wang, Y. Xia, J. Zhang, L. Chen. Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies. Signal Transduction and Targeted Therapy 9 (2024) 211. https://doi.org/10.1038/s41392-024-01911-3 DOI: https://doi.org/10.1038/s41392-024-01911-3

[39] H. Jeong, H. Shin, S. Hong, Y. Kim. Physiological roles of monomeric amyloid-β and implications for Alzheimer’s disease therapeutics. Experimental Neurobiology 31 (2022) 65. https://doi.org/10.5607/en22004 DOI: https://doi.org/10.5607/en22004

[40] K. Iqbal, F. Liu, C.-X. Gong, I. Grundke-Iqbal. Tau in Alzheimer disease and related tauopathies. Current Alzheimer Research 7 (2010) 656-664. https://doi.org/10.2174/156720510793611592 DOI: https://doi.org/10.2174/156720510793611592

[41] M. Alipour, M. Motavaf, P. Abdolmaleki, A. Zali, F. Ashrafi, S. Safari, B. Hajipour-Verdom. Structural analysis and conformational dynamics of Short helical hyperphosphorylated segments of tau protein (sequence 254–290) in alzheimer’s disease: a molecular dynamics simulation study. Frontiers in Molecular Biosciences 9 (2022) 884705. https://doi.org/10.3389/fmolb.2022.884705 DOI: https://doi.org/10.3389/fmolb.2022.884705

[42] L. Song, D.E. Oseid, E.A. Wells, A.S. Robinson. The Interplay between GSK3β and Tau Ser262 phosphorylation during the progression of tau pathology. International Journal of Molecular Sciences 23 (2022) 11610. https://doi.org/10.3390/ijms231911610 DOI: https://doi.org/10.3390/ijms231911610

[43] Y. Xia, S. Prokop, B.I. Giasson. “Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies. Molecular Neurodegeneration 16 (2021) 37. https://doi.org/10.1186/s13024-021-00460-5 DOI: https://doi.org/10.1186/s13024-021-00460-5

[44] Z.D. Zhou, L.X. Yi, D.Q. Wang, T.M. Lim, E.K. Tan. Role of dopamine in the pathophysiology of Parkinson’s disease. Translational Neurodegeneration 12 (2023) 44. https://doi.org/10.1186/s40035-023-00378-6 DOI: https://doi.org/10.1186/s40035-023-00378-6

[45] A. Martirosyan, R. Ansari, F. Pestana, K. Hebestreit, H. Gasparyan, R. Aleksanyan, S. Hnatova, S. Poovathingal, C. Marneffe, D.R. Thal. Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution. Molecular Neurodegeneration 19 (2024) 1-24. https://doi.org/10.1186/s13024-023-00699-0 DOI: https://doi.org/10.1186/s13024-024-00717-9

[46] J. Pitton Rissardo, A. McGarry, Y. Shi, A.L. Fornari Caprara, G.T. Kannarkat. Alpha-Synuclein Neurobiology in Parkinson’s Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives. Brain Sciences 15 (2025) 1260. https://doi.org/10.3390/brainsci15121260 DOI: https://doi.org/10.3390/brainsci15121260

[47] C.A. Morato Torres, Z. Wassouf, F. Zafar, D. Sastre, T.F. Outeiro, B. Schüle. The role of alpha-synuclein and other Parkinson’s genes in neurodevelopmental and neurodegenerative disorders. International Journal of Molecular Sciences 21 (2020) 5724. https://doi.org/10.3390/ijms21165724 DOI: https://doi.org/10.3390/ijms21165724

[48] M. Alipour, B. Hajipour-Verdom, A. Zali, F. Ashrafi, P. Abdolmaleki, S. Oraee-Yazdani, M. Akhlaghdoust, N. Karimi. Interaction of α-synuclein with DJ-1 in homodimer and L166P mutant monomer forms in Parkinson’s disease: a molecular dynamics study. Journal of Biomolecular Structure and Dynamics 44 (2024) 1558-1565. https://doi.org/10.1080/07391102.2024.2446660 DOI: https://doi.org/10.1080/07391102.2024.2446660

[49] N. Ramalingam, U. Dettmer. α-Synuclein serine129 phosphorylation–the physiology of pathology. Molecular neurodegeneration 18 (2023) 84. https://doi.org/10.1186/s13024-023-00680-x DOI: https://doi.org/10.1186/s13024-023-00680-x

[50] K. Beyer, A. Ariza. alpha-Synuclein posttranslational modification and alternative splicing as a trigger for neurodegeneration. Molecular Neurobiology 47 (2013) 509-524. https://doi.org/10.1007/s12035-012-8330-5 DOI: https://doi.org/10.1007/s12035-012-8330-5

[51] R. Andrews, B. Fu, C.E. Toomey, J.C. Breiter, J. Lachica, J.S. Beckwith, R. Tian, E.E. Brock, L.-M. Needham, G.J. Chant. Large-scale visualization of α-synuclein oligomers in Parkinson’s disease brain tissue. Nature Biomedical Engineering (2025). https://doi.org/10.1038/s41551-025-01496-4 DOI: https://doi.org/10.1038/s41551-025-01496-4

[52] A. Bigi, R. Cascella, C. Cecchi. α-Synuclein oligomers and fibrils: partners in crime in synucleinopathies. Neural Regeneration Research 18 (2023) 2332-2342. https://doi.org/10.4103/1673-5374.371345 DOI: https://doi.org/10.4103/1673-5374.371345

[53] F.N. Emamzadeh. Alpha-synuclein structure, functions, and interactions. Journal of Research in Medical Sciences 21 (2016) 29. https://doi.org/10.4103/1735-1995.181989 DOI: https://doi.org/10.4103/1735-1995.181989

[54] T. Tripathi. A master regulator of α-synuclein aggregation. ACS Chemical Neuroscience 11 (2020) 1376-1378. https://doi.org/10.1021/acschemneuro.0c00216 DOI: https://doi.org/10.1021/acschemneuro.0c00216

[55] N. Exner, A.K. Lutz, C. Haass, K.F. Winklhofer. Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences. The EMBO Journal 31 (2012) 3038-3062. https://doi.org/10.1038/emboj.2012.170 DOI: https://doi.org/10.1038/emboj.2012.170

[56] S. Miller, M.M. Muqit. Therapeutic approaches to enhance PINK1/Parkin mediated mitophagy for the treatment of Parkinson’s disease. Neuroscience Letters 705 (2019) 7-13. https://doi.org/10.1016/j.neulet.2019.04.029 DOI: https://doi.org/10.1016/j.neulet.2019.04.029

[57] J. Zhang, X. Li, J.-D. Li. The roles of post-translational modifications on α-synuclein in the pathogenesis of Parkinson’s diseases. Frontiers in Neuroscience 13 (2019) 381. https://doi.org/10.3389/fnins.2019.00381 DOI: https://doi.org/10.3389/fnins.2019.00381

[58] S. Sahoo, A.A. Padhy, V. Kumari, P. Mishra. Role of ubiquitin–proteasome and autophagy-lysosome pathways in α-synuclein aggregate clearance. Molecular Neurobiology 59 (2022) 5379-5407. https://doi.org/10.1007/s12035-022-02897-1 DOI: https://doi.org/10.1007/s12035-022-02897-1

[59] I. Stojkovska, D. Krainc, J.R. Mazzulli. Molecular mechanisms of α-synuclein and GBA1 in Parkinson’s disease. Cell and Tissue Research 373 (2018) 51-60. https://doi.org/10.1007/s00441-017-2704-y DOI: https://doi.org/10.1007/s00441-017-2704-y

[60] K. Wakabayashi, K. Tanji, S. Odagiri, Y. Miki, F. Mori, H. Takahashi. The Lewy body in Parkinson’s disease and related neurodegenerative disorders. Molecular Neurobiology 47 (2013) 495-508. https://doi.org/10.1007/s12035-012-8280-y DOI: https://doi.org/10.1007/s12035-012-8280-y

[61] D. Sulzer, R.H. Edwards. The physiological role of α‐synuclein and its relationship to Parkinson’s disease. Journal of Neurochemistry 150 (2019) 475-486. https://doi.org/10.1111/jnc.14810 DOI: https://doi.org/10.1111/jnc.14810

[62] S. Del Sol-Fernández, P. Martínez-Vicente, P. Gomollón-Zueco, C. Castro-Hinojosa, L. Gutiérrez, R.M. Fratila, M. Moros. Magnetogenetics: remote activation of cellular functions triggered by magnetic switches. Nanoscale 14 (2022) 2091-2118. https://doi.org/10.1039/d1nr06303k DOI: https://doi.org/10.1039/D1NR06303K

[63] S. Qin, H. Yin, C. Yang, Y. Dou, Z. Liu, P. Zhang, H. Yu, Y. Huang, J. Feng, J. Hao. A magnetic protein biocompass. Nature Materials 15 (2016) 217-226. https://doi.org/10.1038/nmat4484 DOI: https://doi.org/10.1038/nmat4484

[64] S.A. Stanley, J. Sauer, R.S. Kane, J.S. Dordick, J.M. Friedman. Remote regulation of glucose homeostasis in mice using genetically encoded nanoparticles. Nature Medicine 21 (2015) 92-98. https://doi.org/10.1038/nm.3730 DOI: https://doi.org/10.1038/nm.3730

[65] S.A. Ralph, G.G. Van Dooren, R.F. Waller, M.J. Crawford, M.J. Fraunholz, B.J. Foth, C.J. Tonkin, D.S. Roos, G.I. McFadden. Metabolic maps and functions of the Plasmodium falciparum apicoplast. Nature Reviews Microbiology 2 (2004) 203-216. https://doi.org/10.1038/nrmicro843 DOI: https://doi.org/10.1038/nrmicro843

[66] D. Schüler. Magnetoreception and magnetosomes in bacteria. Springer-Verlag, Berlin, Germany (2006). https://doi.org/10.1007/11741862 DOI: https://doi.org/10.1007/11741862

[67] P.J. Hore, H. Mouritsen. The radical-pair mechanism of magnetoreception. Annual Review of Biophysics 45 (2016) 299-344. https://doi.org/10.1146/annurev-biophys-032116-094545 DOI: https://doi.org/10.1146/annurev-biophys-032116-094545

[68] H. Huang, S. Delikanli, H. Zeng, D.M. Ferkey, A. Pralle. Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. Nature Nanotechnology 5 (2010) 602-606. https://doi.org/10.1038/nnano.2010.125 DOI: https://doi.org/10.1038/nnano.2010.125

[69] R.J. Gegear, A. Casselman, S. Waddell, S.M. Reppert. Cryptochrome mediates light-dependent magnetosensitivity in Drosophila. Nature 454 (2008) 1014-1018. https://doi.org/10.1038/nature07183 DOI: https://doi.org/10.1038/nature07183

[70] I. Chaves, R. Pokorny, M. Byrdin, N. Hoang, T. Ritz, K. Brettel, L.-O. Essen, G.T. Van Der Horst, A. Batschauer, M. Ahmad. The cryptochromes: blue light photoreceptors in plants and animals. Annual Review of Plant Biology 62 (2011) 335-364. https://doi.org/10.1146/annurev-arplant-042110-103759 DOI: https://doi.org/10.1146/annurev-arplant-042110-103759

[71] K.J. Lohmann. A candidate magnetoreceptor. Nature Materials 15 (2016) 136-138. https://doi.org/10.1038/nmat4550 DOI: https://doi.org/10.1038/nmat4550

[72] K. Maeda, A.J. Robinson, K.B. Henbest, H.J. Hogben, T. Biskup, M. Ahmad, E. Schleicher, S. Weber, C.R. Timmel, P.J. Hore. Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor. Proceedings of the National Academy of Sciences 109 (2012) 4774-4779. https://doi.org/10.1073/pnas.1118959109 DOI: https://doi.org/10.1073/pnas.1118959109

[73] C.A. Dodson, P.J. Hore, M.I. Wallace. A radical sense of direction: signalling and mechanism in cryptochrome magnetoreception. Trends in Biochemical Sciences 38 (2013) 435-446. https://doi.org/10.1016/j.tibs.2013.07.002 DOI: https://doi.org/10.1016/j.tibs.2013.07.002

[74] M.A. Gauger, A. Sancar. Cryptochrome, circadian cycle, cell cycle checkpoints, and cancer. Cancer Research 65 (2005) 6828-6834. https://doi.org/10.1158/0008-5472.can-05-1119 DOI: https://doi.org/10.1158/0008-5472.CAN-05-1119

[75] H. Yu, X. Meng, J. Wu, C. Pan, X. Ying, Y. Zhou, R. Liu, W. Huang. Cryptochrome 1 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer. PloS One 8 (2013) e61679. https://doi.org/10.1371/journal.pone.0061679 DOI: https://doi.org/10.1371/journal.pone.0061679

[76] F.C. Kelleher, A. Rao, A. Maguire. Circadian molecular clocks and cancer. Cancer Letters 342 (2014) 9-18. https://doi.org/10.1016/j.canlet.2013.09.040 DOI: https://doi.org/10.1016/j.canlet.2013.09.040

[77] G. Fedele, M.D. Edwards, S. Bhutani, J.M. Hares, M. Murbach, E.W. Green, S. Dissel, M.H. Hastings, E. Rosato, C.P. Kyriacou. Genetic analysis of circadian responses to low frequency electromagnetic fields in Drosophila melanogaster. PLoS Genetics 10 (2014) e1004804. https://doi.org/10.1371/journal.pgen.1004804 DOI: https://doi.org/10.1371/journal.pgen.1004804

[78] R. Marley, C.N. Giachello, N.S. Scrutton, R.A. Baines, A.R. Jones. Cryptochrome-dependent magnetic field effect on seizure response in Drosophila larvae. Scientific Reports 4 (2014) 5799. https://doi.org/10.1038/srep05799 DOI: https://doi.org/10.1038/srep05799

[79] T. Ritz, S. Adem, K. Schulten. A model for photoreceptor-based magnetoreception in birds. Biophysical Journal 78 (2000) 707-718. https://doi.org/10.1016/s0006-3495(00)76629-x DOI: https://doi.org/10.1016/S0006-3495(00)76629-X

[80] R. Wiltschko, P. Thalau, D. Gehring, C. Nießner, T. Ritz, W. Wiltschko. Magnetoreception in birds: the effect of radio-frequency fields. Journal of the Royal Society Interface 12 (2015) 20141103. https://doi.org/10.1098/rsif.2014.1103 DOI: https://doi.org/10.1098/rsif.2014.1103

[81] H. Mouritsen. Long-distance navigation and magnetoreception in migratory animals. Nature 558 (2018) 50-59. https://doi.org/10.1038/s41586-018-0176-1 DOI: https://doi.org/10.1038/s41586-018-0176-1

[82] D.R. Kattnig, E.W. Evans, V. Déjean, C.A. Dodson, M.I. Wallace, S.R. Mackenzie, C.R. Timmel, P. Hore. Chemical amplification of magnetic field effects relevant to avian magnetoreception. Nature Chemistry 8 (2016) 384-391. https://doi.org/10.1038/nchem.2447 DOI: https://doi.org/10.1038/nchem.2447

[83] C.T. Rodgers, P.J. Hore. Chemical magnetoreception in birds: the radical pair mechanism. Proceedings of the National Academy of Sciences 106 (2009) 353-360. https://doi.org/10.1073/pnas.0711968106 DOI: https://doi.org/10.1073/pnas.0711968106

[84] C. Feillet, G.T. van Der Horst, F. Levi, D.A. Rand, F. Delaunay. Coupling between the circadian clock and cell cycle oscillators: implication for healthy cells and malignant growth. Frontiers in Neurology 6 (2015) 96. https://doi.org/10.3389/fneur.2015.00096 DOI: https://doi.org/10.3389/fneur.2015.00096

[85] N. Ozturk, D. Ozturk, I. Halil Kavakli, A. Okyar. Molecular aspects of circadian pharmacology and relevance for cancer chronotherapy. International Journal of Molecular Sciences 18 (2017) 2168. https://doi.org/10.3390/ijms18102168 DOI: https://doi.org/10.3390/ijms18102168

[86] A. Sancar, R.N. Van Gelder. Clocks, cancer, and chronochemotherapy. Science 371 (2021) eabb0738. https://doi.org/10.1126/science.abb0738 DOI: https://doi.org/10.1126/science.abb0738

[87] R.M. Sherrard, N. Morellini, N. Jourdan, M. El-Esawi, L.-D. Arthaut, C. Niessner, F. Rouyer, A. Klarsfeld, M. Doulazmi, J. Witczak. Low-intensity electromagnetic fields induce human cryptochrome to modulate intracellular reactive oxygen species. PLoS Biology 16 (2018) e2006229. https://doi.org/10.1371/journal.pbio.2006229 DOI: https://doi.org/10.1371/journal.pbio.2006229

[88] P. Boesch, F. Weber-Lotfi, N. Ibrahim, V. Tarasenko, A. Cosset, F. Paulus, R.N. Lightowlers, A. Dietrich. DNA repair in organelles: pathways, organization, regulation, relevance in disease and aging. Biochimica et Biophysica Acta-Molecular Cell Research 1813 (2011) 186-200. https://doi.org/10.1016/j.bbamcr.2010.10.002 DOI: https://doi.org/10.1016/j.bbamcr.2010.10.002

[89] T. Helleday, E. Petermann, C. Lundin, B. Hodgson, R.A. Sharma. DNA repair pathways as targets for cancer therapy. Nature Reviews Cancer 8 (2008) 193-204. https://doi.org/10.1038/nrc2342 DOI: https://doi.org/10.1038/nrc2342

[90] C.N. Giachello, N.S. Scrutton, A.R. Jones, R.A. Baines. Magnetic fields modulate blue-light-dependent regulation of neuronal firing by cryptochrome. Journal of Neuroscience 36 (2016) 10742-10749. https://doi.org/10.1523/jneurosci.2140-16.2016 DOI: https://doi.org/10.1523/JNEUROSCI.2140-16.2016

[91] A. Shostak. Circadian clock, cell division, and cancer: from molecules to organism. International Journal of Molecular Sciences 18 (2017) 873. https://doi.org/10.3390/ijms18040873 DOI: https://doi.org/10.3390/ijms18040873

[92] A. Sancar, L.A. Lindsey-Boltz, T.-H. Kang, J.T. Reardon, J.H. Lee, N. Ozturk. Circadian clock control of the cellular response to DNA damage. FEBS Letters 584 (2010) 2618-2625. https://doi.org/10.1016/j.febslet.2010.03.017 DOI: https://doi.org/10.1016/j.febslet.2010.03.017

[93] B.A. Carneiro, W.S. El-Deiry. Targeting apoptosis in cancer therapy. Nature Reviews Clinical Oncology 17 (2020) 395-417. https://doi.org/10.1038/s41571-020-0341-y DOI: https://doi.org/10.1038/s41571-020-0341-y

[94] J. Qiu, T. Dai, H. Tao, X. Li, C. Luo, Y. Sima, S. Xu. Inhibition of expression of the circadian clock gene cryptochrome 1 causes abnormal glucometabolic and cell growth in Bombyx mori Cells. International Journal of Molecular Sciences 24 (2023) 5435. https://doi.org/10.3390/ijms24065435 DOI: https://doi.org/10.3390/ijms24065435

[95] K.H.C. Baser, I.C. Haskologlu, E. Erdag. Molecular links between circadian rhythm disruption, melatonin, and neurodegenerative diseases: an updated review. Molecules 30 (2025) 1888. https://doi.org/10.3390/molecules30091888 DOI: https://doi.org/10.3390/molecules30091888

[96] V.S. Sukhorukov, N.M. Mudzhiri, A.S. Voronkova, T.I. Baranich, V.V. Glinkina, S.N. Illarioshkin. Mitochondrial disorders in Alzheimer’s disease. Biochemistry (Moscow) 86 (2021) 667-679. https://doi.org/10.1134/s0006297921060055 DOI: https://doi.org/10.1134/S0006297921060055

[97] C. Suárez-Barrio, S. del Olmo-Aguado, E. García-Pérez, M. de la Fuente, F. Muruzabal, E. Anitua, B. Baamonde-Arbaiza, L. Fernández-Vega-Cueto, L. Fernández-Vega, J. Merayo-Lloves. Antioxidant role of PRGF on RPE cells after blue light insult as a therapy for neurodegenerative diseases. International Journal of Molecular Sciences 21 (2020) 1021. https://doi.org/10.3390/ijms21031021 DOI: https://doi.org/10.3390/ijms21031021

[98] E. Mitroshina, E. Kalinina, M. Vedunova. Optogenetics in Alzheimer’s disease: focus on astrocytes. Antioxidants 12 (2023) 1856. https://doi.org/10.3390/antiox12101856 DOI: https://doi.org/10.3390/antiox12101856

[99] B.H. Correa, C.R. Moreira, M.E. Hildebrand, L.B. Vieira. The role of voltage-gated calcium channels in basal ganglia neurodegenerative disorders. Current Neuropharmacology 21 (2023) 183-201. https://doi.org/10.2174/1570159x20666220327211156 DOI: https://doi.org/10.2174/1570159X20666220327211156

[100] C. Cheignon, F. Collin, L. Sabater, C. Hureau. Oxidative damages on the Alzheimer’s related-Aβ peptide alters its ability to assemble. Antioxidants 12 (2023) 472. https://doi.org/10.3390/antiox12020472 DOI: https://doi.org/10.3390/antiox12020472

[101] M. Gu, D.C. Bode, J.H. Viles. Copper redox cycling inhibits Aβ fibre formation and promotes fibre fragmentation, while generating a dityrosine Aβ dimer. Scientific Reports 8 (2018) 16190. https://doi.org/10.1038/s41598-018-33935-5 DOI: https://doi.org/10.1038/s41598-018-33935-5

[102] S.R. D’Mello. When good kinases go rogue: GSK3, p38 MAPK and CDKs as therapeutic targets for Alzheimer’s and Huntington’s disease. International Journal of Molecular Sciences 22 (2021) 5911. https://doi.org/10.3390/ijms22115911 DOI: https://doi.org/10.3390/ijms22115911

[103] S. Somin, D. Kulasiri, S. Samarasinghe. Alleviating the unwanted effects of oxidative stress on Aβ clearance: a review of related concepts and strategies for the development of computational model-ling. Translational Neurodegeneration 12 (2023) 11. https://doi.org/10.1186/s40035-023-00344-2 DOI: https://doi.org/10.1186/s40035-023-00344-2

[104] V. Pillai, L. Buck, E. Lari. Scavenging of reactive oxygen species mimics the anoxic response in goldfish pyramidal neurons. Journal of Experimental Biology 224 (2021) jeb238147. https://doi.org/10.1242/jeb.238147 DOI: https://doi.org/10.1242/jeb.238147

[105] M. Alipour, M. Abdolmaleki, Y. Shabanpour, A. Zali, F. Ashrafi, S. Nohesara, B. Hajipour-Verdom. Advances in magnetic field approaches for non-invasive targeting neuromodulation. Frontiers in Human Neuroscience 19 (2025) 1489940. https://doi.org/10.3389/fnhum.2025.1489940 DOI: https://doi.org/10.3389/fnhum.2025.1489940

[106] K.R. Hoyt, K. Obrietan. Circadian clocks, cognition, and Alzheimer’s disease: synaptic mechanisms, signaling effectors, and chronotherapeutics. Molecular Neurodegeneration 17 (2022) 35. https://doi.org/10.1186/s13024-022-00537-9 DOI: https://doi.org/10.1186/s13024-022-00537-9

[107] C. Xu, Y. Lv, C. Chen, Y. Zhang, S. Wei. Blue light-dependent phosphorylations of cryptochromes are affected by magnetic fields in Arabidopsis. Advances in Space Research 53 (2014) 1118-1124. https://doi.org/10.1016/j.asr.2014.01.033 DOI: https://doi.org/10.1016/j.asr.2014.01.033

[108] H. Zadeh-Haghighi, C. Simon. Radical pairs can explain magnetic field and lithium effects on the circadian clock. Scientific Reports 12 (2022) 269. https://doi.org/10.1038/s41598-021-04334-0 DOI: https://doi.org/10.1038/s41598-021-04334-0

[109] L. Zhang, E.P. Malkemper. Cryptochromes in mammals: a magnetoreception misconception? Frontiers in Physiology 14 (2023) 1250798. https://doi.org/10.3389/fphys.2023.1250798 DOI: https://doi.org/10.3389/fphys.2023.1250798

[110] G. Minakaki, D. Krainc, L.F. Burbulla. The convergence of alpha-synuclein, mitochondrial, and lysosomal pathways in vulnerability of midbrain dopaminergic neurons in Parkinson’s disease. Frontiers in Cell and Developmental Biology 8 (2020) 580634. https://doi.org/10.3389/fcell.2020.580634 DOI: https://doi.org/10.3389/fcell.2020.580634

[111] M. Yalçin, V. Grande, T.F. Outeiro, A. Relógio. Circadian clock dysfunction in Parkinson’s disease: mechanisms, consequences, and therapeutic strategy. npj Parkinson's Disease 11 (2025) 213. https://doi.org/10.1038/s41531-025-01009-9 DOI: https://doi.org/10.1038/s41531-025-01009-9

[112] R. Rishabh, H. Zadeh-Haghighi, D. Salahub, C. Simon. Radical pairs may explain reactive oxygen species-mediated effects of hypomagnetic field on neurogenesis. PLOS Computational Biology 18 (2022) e1010198. https://doi.org/10.1371/journal.pcbi.1010198 DOI: https://doi.org/10.1371/journal.pcbi.1010198

[113] K.M. Ricke, T. Paß, S. Kimoloi, K. Fährmann, C. Jüngst, A. Schauss, O.R. Baris, M. Aradjanski, A. Trifunovic, T.M.E. Faelker. Mitochondrial dysfunction combined with high calcium load leads to impaired antioxidant defense underlying the selective loss of nigral dopaminergic neurons. Journal of Neuroscience 40 (2020) 1975-1986. https://doi.org/10.1523/jneurosci.1345-19.2019 DOI: https://doi.org/10.1523/JNEUROSCI.1345-19.2019

[114] A. Bose, M.F. Beal. Mitochondrial dysfunction in Parkinson's disease. Journal of Neurochemistry 139 (2016) 216-231. https://doi.org/10.1111/jnc.13731 DOI: https://doi.org/10.1111/jnc.13731

[115] S.J. Chinta, J.K. Mallajosyula, A. Rane, J.K. Andersen. Mitochondrial alpha-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy in vivo. Neuroscience Letters 486 (2010) 235-239. https://doi.org/10.1016/j.neulet.2010.09.061 DOI: https://doi.org/10.1016/j.neulet.2010.09.061

[116] I. Kawahata, D.I. Finkelstein, K. Fukunaga. Pathogenic impact of α-synuclein phosphorylation and its kinases in α-synucleinopathies. International Journal of Molecular Sciences 23 (2022) 6216. https://doi.org/10.3390/ijms23116216 DOI: https://doi.org/10.3390/ijms23116216

[117] J. Wu, H. Lou, T.N. Alerte, E.K. Stachowski, J. Chen, A.B. Singleton, R.L. Hamilton, R.G. Perez. Lewy-like aggregation of α-synuclein reduces protein phosphatase 2A activity in vitro and in vivo. Neuroscience 207 (2012) 288-297. https://doi.org/10.1016/j.neuroscience.2012.01.028 DOI: https://doi.org/10.1016/j.neuroscience.2012.01.028

[118] D. Ebrahimi-Fakhari, L. Wahlster, P.J. McLean. Protein degradation pathways in Parkinson’s disease: curse or blessing. Acta Neuropathologica 124 (2012) 153-172. https://doi.org/10.1007/s00401-012-1004-6 DOI: https://doi.org/10.1007/s00401-012-1004-6

[119] K. Xu, Y. Zhang, Y. Shi, Y. Zhang, C. Zhang, T. Wang, P. Lv, Y. Bai, S. Wang. Circadian rhythm disruption: a potential trigger in Parkinson’s disease pathogenesis. Frontiers in Cellular Neuroscience 18 (2024) 1464595. https://doi.org/10.3389/fncel.2024.1464595 DOI: https://doi.org/10.3389/fncel.2024.1464595

[120] T. Yoshii, M. Ahmad, C. Helfrich-Förster. Cryptochrome mediates light-dependent magnetosensitivity of Drosophila's circadian clock. PLoS Biology 7 (2009) e1000086. https://doi.org/10.1371/journal.pbio.1000086 DOI: https://doi.org/10.1371/journal.pbio.1000086