MOLECULAR MECHANISMS OF NEURODEGENERATIVE DISEASES

Main Article Content

Otaboyeva Marvarid Sodiqovna,Qo'ziboyeva Shahzoda Isomiddin kizi, Mansurova D. A

Abstract

 Neurodegenerative diseases are progressive and irreversible disorders of the central nervous system characterized by neuronal death and functional dysfunction. According to the World Health Organization (WHO), in 2023, neurodegenerative diseases affected more than 55 million people worldwide and are among the leading causes of disability and death. Alzheimer’s disease alone accounts for over 50 million cases (WHO, 2023). This article analyzes the molecular mechanisms of major neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and Amyotrophic Lateral Sclerosis (ALS). The main molecular bases of these diseases include protein aggregation, oxidative stress, mitochondrial dysfunction, neuroinflammation, and genetic factors. The article provides an extensive overview of each mechanism supported by scientific data and statistical indicators, aiming to enhance the understanding of neurodegenerative processes. Research indicates that these mechanisms are interrelated and co-occur in approximately 80–90% of cases (Alzheimer’s Association, 2022).

Downloads

Download data is not yet available.

Article Details

Section

Articles

How to Cite

MOLECULAR MECHANISMS OF NEURODEGENERATIVE DISEASES. (2025). Journal of Multidisciplinary Sciences and Innovations, 4(9), 317-322. https://doi.org/10.55640/

References

1.Alzheimer’s Association. (2022). Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 18(4), 700–789. https://doi.org/10.1002/alz.12638

2.Bossy-Wetzel, E., Petrilli, A., & Knott, A. B. (2008). Mitochondrial fission in Huntington’s disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1802(10), 552–563. https://doi.org/10.1016/j.bbadis.2008.04.012

3.Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., ... Pericak-Vance, M. A. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late-onset families.Science, 261(5123), 921–923. https://doi.org/10.1126/science.8346443

4.Cummings, J., Lee, G., Zhong, K., Fonseca, J., & Taghva, K. (2021).

5.Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for Alzheimer’s disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1772(2), 135–146. https://doi.org/10.1016/j.bbadis.2006.07.017

6.Alzheimer's & Dementia: Translational Research & Clinical Interventions. (2021). 7(1), e12179. https://doi.org/10.1002/trc2.12179

7.De Jager, P. L., Srivastava, G., Lunnon, K., Burgess, J., Schalkwyk, L. C., Chen, K., ... Bennett, D. A. (2014). Alzheimer’s disease: Early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nature Neuroscience, 17(9), 1156–1163. https://doi.org/10.1038/nn.3786

8.Fahn, S., & Sulzer, D. (2004). Neuroprotection and dopamine agonists. Neurology, 62(8 Suppl 2), S1–S8. https://doi.org/10.1212/WNL.62.8_suppl_2.S1

9.Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010). Mechanisms underlying inflammation in neurodegeneration. Cell, 140(6), 918–934. https://doi.org/10.1016/j.cell.2010.02.016

10.Halliwell, B. (2006). Oxidative stress and neurodegeneration: Where are we now? Journal of Neurochemistry, 97(6), 1634–1658. https://doi.org/10.1111/j.1471-4159.2006.03907.x

11.Heneka, M. T., Carson, M. J., El Khoury, J., Landau, S. M., Brosnan, C. F., Feinstein, D. L., ... Kummer, M. P. (2015). Neuroinflammation in Alzheimer’s disease. The Lancet Neurology, 14(4), 388–405. https://doi.org/10.1016/S1474-4422(15)70016-5

12.In ’t Veld, B. A., Ruitenberg, A., Hofman, A., Launer, L. J., van Duijn, C. M., Stijnen, T., ... Stricker, B. H. (2001). Nonsteroidal anti-inflammatory drugs and the risk of Alzheimer’s disease. New England Journal of Medicine, 345(21), 1515–1521. https://doi.org/10.1056/NEJMoa010178

13.Klein, C., & Westenberger, A. (2012). Genetics of Parkinson’s disease. Cold Spring Harbor Perspectives in Medicine, 2(1), a008888. https://doi.org/10.1101/cshperspect.a008888

14.Labbé, C., Lorenzo-Betancor, O., & Farrer, M. J. (2016). Insights into genetic susceptibility to Parkinson’s disease from genome-wide association studies. Cold Spring Harbor Perspectives in Medicine, 6(3), a024299. https://doi.org/10.1101/cshperspect.a024299

15.Lin, M. T., & Beal, M. F. (2006). Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 443(7113), 787–795. https://doi.org/10.1038/nature05292

16.MacDonald, M. E., Ambrose, C. M., Duyao, M. P., Myers, R. H., Lin, C., Srinidhi, L., ... Gusella, J. F. (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell, 72(6), 971–983. https://doi.org/10.1016/0092-8674(93)90585-E

17.Markesbery, W. R. (1997). Oxidative stress hypothesis in Alzheimer’s disease. Free Radical Biology and Medicine, 23(1), 134–147. https://doi.org/10.1016/S0891-5849(96)00629-6

18.Matthews, R. T., Yang, L., Browne, S. E., Baik, M., & Beal, M. F. (1998). Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proceedings of the National Academy of Sciences, 95(15), 8892–8897. https://doi.org/10.1073/pnas.95.15.8892

19.McGeer, P. L., & McGeer, E. G. (2008). Glial reactions in Parkinson’s disease. Movement Disorders, 23(4), 474–483. https://doi.org/10.1002/mds.21860

20.Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., ... Lee, V. M. (2006). Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science, 314(5796), 130–133. https://doi.org/10.1126/science.1134108

21.Parkinson’s Foundation. (2023). Statistics. Retrieved from https://www.parkinson.org/understanding-parkinsons/statistics

22.Philips, T., & Robberecht, W. (2011). Neuroinflammation in amyotrophic lateral sclerosis: Role of glial activation in motor neuron disease. The Lancet Neurology, 10(3), 253–263. https://doi.org/10.1016/S1474-4422(10)70290-1

23.Przedborski, S., Vila, M., & Jackson-Lewis, V. (2003). Neurodegeneration: What is it and where are we? Journal of Clinical Investigation, 111(1), 3–10. https://doi.org/10.1172/JCI200318782

24.Qureshi, I. A., & Mehler, M. F. (2014). Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases. Neurobiology of Disease, 39(1), 15–24. https://doi.org/10.1016/j.nbd.2009.12.001

Reddy, P. H., & Beal, M. F. (2008).

25.Mitochondrial dysfunction in neurodegenerative diseases: Cause and consequence. (2008). Journal of Bioenergetics and Biomembranes, 40(5), 421–422. https://doi.org/10.1007/s10863-008-9169-6

26.Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., ... Traynor, B. J. (2011). A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron, 72(2), 257–268. https://doi.org/10.1016/j.neuron.2011.09.010

27.Roos, R. A. C. (2010). Huntington’s disease: A clinical review. Orphanet Journal of Rare Diseases, 5(1), 40. https://doi.org/10.1186/1750-1172-5-40

28.Ross, C. A., & Poirier, M. A. (2004). Protein aggregation and neurodegenerative disease. Nature Medicine, 10(7 Suppl), S10–S17. https://doi.org/10.1038/nm1066

29.Ross, C. A., & Tabrizi, S. J. (2011). Huntington’s disease: From molecular pathogenesis to clinical treatment. The Lancet Neurology, 10(1), 83–98. https://doi.org/10.1016/S1474-4422(10)70245-3

30.Saeed, U., Lang, A. E., & Darvesh, S. (2016). Differences in Parkinson’s disease risk between African Americans and Whites: A systematic review and meta-analysis. Movement Disorders, 31(12), 1749–1759. https://doi.org/10.1002/mds.26800

31.Schapira, A. H., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P., & Marsden, C. D. (1990). Mitochondrial complex I deficiency in Parkinson’s disease. Journal of Neurochemistry, 54(3), 823–827. https://doi.org/10.1111/j.1471-4159.1990.tb02325.x

32.Selkoe, D. J. (2001). Alzheimer’s disease: Genes, proteins, and therapy. Physiological Reviews, 81(2), 741–766. https://doi.org/10.1152/physrev.2001.81.2.741

33.Shi, P., Wei, Y., Zhang, J., Chen, Y., & Xu, D. (2010). Mitochondrial dysfunction is induced by cytosolic TDP-43 accumulation in ALS. Brain Research, 1348, 174–182. https://doi.org/10.1016/j.brainres.2010.06.019

34.Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997). Alpha-synuclein in Lewy bodies. Nature, 388(6645), 839–840. https://doi.org/10.1038/42166

35.World Health Organization (WHO). (2023). Dementia fact sheet. Retrieved from https://www.who.int/news-room/fact-sheets/detail/dementia

Similar Articles

You may also start an advanced similarity search for this article.