Oxidative Stress, Mitochondrial Damage and Neurodegenerative Diseases

Overview

Journal Neural Regen Res

Date 2014 Sep 11

PMID 25206509

Citations 559

Authors

Chunyan Guo

Li Sun

Xueping Chen

Danshen Zhang

Affiliations

Soon will be listed here.

Abstract

Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca(2+) homeostasis and mitochondrial defense systems. All these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative eases and discusses strategies to modify mitochondrial dysfunction that may be attractive therapeutic interventions for the treatment of various neurodegenerative diseases.

Citing Articles

The effects of concurrent alpha-linolenic acid, L-carnitine supplementation on clinical symptoms, mental health, and quality of life in women with migraine: a randomized, triple-blind, placebo-controlled trial.

Golpour-Hamedani S, Bagherniya M, Khorvash F, Feizi A, Sharma M, Askari G Nutr J. 2025; 24(1):40.

PMID: 40082970 PMC: 11905556. DOI: 10.1186/s12937-025-01107-7.

Mitochondrial transplantation via injection of exogenous mitochondria into blood reduces bleomycin-induced oxidative damages and mitochondrial dysfunction in lung tissue.

Salimi A, Shabani M, Shahsavar S, Naserian A, Khezri S, Karroubian H J Mol Histol. 2025; 56(2):104.

PMID: 40063258 DOI: 10.1007/s10735-025-10386-7.

Neuro-Nutrition and Exercise Synergy: Exploring the Bioengineering of Cognitive Enhancement and Mental Health Optimization.

Clemente-Suarez V, Martin-Rodriguez A, Curiel-Regueros A, Rubio-Zarapuz A, Tornero-Aguilera J Bioengineering (Basel). 2025; 12(2).

PMID: 40001727 PMC: 11851474. DOI: 10.3390/bioengineering12020208.

Flavonolignans silybin, silychristin and 2,3-dehydrosilybin showed differential cytoprotective, antioxidant and anti-apoptotic effects on splenocytes from Balb/c mice.

Jurcackova Z, Hrckova G, Mudronova D, Matiasova A, Biedermann D Sci Rep. 2025; 15(1):5631.

PMID: 39955331 PMC: 11830019. DOI: 10.1038/s41598-025-89824-1.

The Effect of Picein on Inhibitory Avoidance Memory and Activity of Antioxidant Enzymes in Hippocampus of Male Rats with Scopolamine-Induced Injury.

Elyasi L, Rosenholm J, Jahanshahi M, Jesmi F Mol Neurobiol. 2025; .

PMID: 39946000 DOI: 10.1007/s12035-025-04740-9.

References

Horowitz M, Greenamyre J . Gene-environment interactions in Parkinson's disease: the importance of animal modeling. Clin Pharmacol Ther. 2010; 88(4):467-74. PMC: 3085510. DOI: 10.1038/clpt.2010.138. View

Martin L . The mitochondrial permeability transition pore: a molecular target for amyotrophic lateral sclerosis therapy. Biochim Biophys Acta. 2009; 1802(1):186-97. PMC: 2790555. DOI: 10.1016/j.bbadis.2009.07.009. View

Ferreiro E, Baldeiras I, Ferreira I, Costa R, Rego A, Pereira C . Mitochondrial- and endoplasmic reticulum-associated oxidative stress in Alzheimer's disease: from pathogenesis to biomarkers. Int J Cell Biol. 2012; 2012:735206. PMC: 3373122. DOI: 10.1155/2012/735206. View

Manfredi G, Xu Z . Mitochondrial dysfunction and its role in motor neuron degeneration in ALS. Mitochondrion. 2005; 5(2):77-87. DOI: 10.1016/j.mito.2005.01.002. View

Chaturvedi R, Beal M . Mitochondria targeted therapeutic approaches in Parkinson's and Huntington's diseases. Mol Cell Neurosci. 2012; 55:101-14. DOI: 10.1016/j.mcn.2012.11.011. View

Qu J, Nakamura T, Holland E, McKercher S, Lipton S . S-nitrosylation of Cdk5: potential implications in amyloid-β-related neurotoxicity in Alzheimer disease. Prion. 2012; 6(4):364-70. PMC: 3609065. DOI: 10.4161/pri.21250. View

Toescu E . Normal brain ageing: models and mechanisms. Philos Trans R Soc Lond B Biol Sci. 2005; 360(1464):2347-54. PMC: 1569594. DOI: 10.1098/rstb.2005.1771. View

Chen J, Yager J, Russo J . Regulation of mitochondrial respiratory chain structure and function by estrogens/estrogen receptors and potential physiological/pathophysiological implications. Biochim Biophys Acta. 2005; 1746(1):1-17. DOI: 10.1016/j.bbamcr.2005.08.001. View

Song S, Jang S, Park J, Bang S, Choi S, Kwon K . Characterization of PINK1 (PTEN-induced putative kinase 1) mutations associated with Parkinson disease in mammalian cells and Drosophila. J Biol Chem. 2013; 288(8):5660-72. PMC: 3581423. DOI: 10.1074/jbc.M112.430801. View

10.

Kirkinezos I, Bacman S, Hernandez D, Oca-Cossio J, Arias L, Perez-Pinzon M . Cytochrome c association with the inner mitochondrial membrane is impaired in the CNS of G93A-SOD1 mice. J Neurosci. 2005; 25(1):164-72. PMC: 6725219. DOI: 10.1523/JNEUROSCI.3829-04.2005. View

11.

Van Houten B, Woshner V, Santos J . Role of mitochondrial DNA in toxic responses to oxidative stress. DNA Repair (Amst). 2005; 5(2):145-52. DOI: 10.1016/j.dnarep.2005.03.002. View

12.

Federoff H . Nur(R1)turing a notion on the etiopathogenesis of Parkinson's disease. Neurotox Res. 2009; 16(3):261-70. DOI: 10.1007/s12640-009-9056-7. View

13.

Anandatheerthavarada H, Biswas G, Robin M, Avadhani N . Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol. 2003; 161(1):41-54. PMC: 2172865. DOI: 10.1083/jcb.200207030. View

14.

Cartier A, Ubhi K, Spencer B, Vazquez-Roque R, Kosberg K, Fourgeaud L . Differential effects of UCHL1 modulation on alpha-synuclein in PD-like models of alpha-synucleinopathy. PLoS One. 2012; 7(4):e34713. PMC: 3326048. DOI: 10.1371/journal.pone.0034713. View

15.

Zivkovic L, Spremo-Potparevic B, Siedlak S, Perry G, Plecas-Solarovic B, Milicevic Z . DNA damage in Alzheimer disease lymphocytes and its relation to premature centromere division. Neurodegener Dis. 2013; 12(3):156-63. DOI: 10.1159/000346114. View

16.

Nicholls D, Budd S . Mitochondria and neuronal survival. Physiol Rev. 2000; 80(1):315-60. DOI: 10.1152/physrev.2000.80.1.315. View

17.

Reddy P, Beal M . Are mitochondria critical in the pathogenesis of Alzheimer's disease?. Brain Res Brain Res Rev. 2005; 49(3):618-32. DOI: 10.1016/j.brainresrev.2005.03.004. View

18.

Sultana R, Poon H, Cai J, Pierce W, Merchant M, Klein J . Identification of nitrated proteins in Alzheimer's disease brain using a redox proteomics approach. Neurobiol Dis. 2005; 22(1):76-87. DOI: 10.1016/j.nbd.2005.10.004. View

19.

Sas K, Robotka H, Toldi J, Vecsei L . Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci. 2007; 257(1-2):221-39. DOI: 10.1016/j.jns.2007.01.033. View

20.

Kumar H, Lim H, More S, Kim B, Koppula S, Kim I . The role of free radicals in the aging brain and Parkinson's Disease: convergence and parallelism. Int J Mol Sci. 2012; 13(8):10478-10504. PMC: 3431873. DOI: 10.3390/ijms130810478. View