Mitochondrial dysfunction: A notable contributor to the progression of Alzheimer's and Parkinson's disease

Olagunju, Abolaji Samson; Ahammad, Foysal; Alagbe, Abiola Adeyanju; Otenaike, Titilayomi Ayomide; Teibo, John Oluwafemi; Mohammad, Farhan; Alsaiari, Ahad Amer; Omotoso, Olabode; Talukder, Md Enamul Kabir

doi:10.1016/j.heliyon.2023.e14387

Cited by 9 publications

(2 citation statements)

References 40 publications

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“…Mitochondria have been implicated in the pathogenesis of neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD) and glaucoma, where their morphological and functional impairments are associated with disease progression [ 43 – 46 ]. Our results agree well with these findings and extend them by showing that mitochondria are not only important in the process of neuronal cell death but also in the recovery of injured neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

PGC-1a mediated mitochondrial biogenesis promotes recovery and survival of neuronal cells from cellular degeneration

You,

Knoops,

Berendschot

et al. 2024

Cell Death Discov.

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Neurodegenerative disorders are characterized by the progressive loss of structure and function of neurons, often including the death of the neuron. Previously, we reported that, by removing the cell death stimulus, dying/injured neurons could survive and recover from the process of regulated cell death, even if the cells already displayed various signs of cellular damage. Now we investigated the role of mitochondrial dynamics (fission/fusion, biogenesis, mitophagy) in both degeneration and in recovery of neuronal cells. In neuronal PC12 cells, exposure to ethanol (EtOH) induced massive neurite loss along with widespread mitochondrial fragmentation, mitochondrial membrane potential loss, reduced ATP production, and decreased total mitochondrial volume. By removing EtOH timely all these mitochondrial parameters recovered to normal levels. Meanwhile, cells regrew neurites and survived. Study of the mitochondrial dynamics showed that autophagy was activated only during the cellular degeneration phase (EtOH treatment) but not in the recovery phase (EtOH removed), and it was not dependent on the Parkin/PINK1 mediated mitophagy pathway. Protein expression of key regulators of mitochondrial fission, phospho-Drp1Ser616 and S-OPA1, increased during EtOH treatment and recovered to normal levels after removing EtOH. In addition, the critical role of PGC-1α mediated mitochondrial biogenesis in cellular recovery was revealed: inhibition of PGC-1α using SR-18292 after EtOH removal significantly impeded recovery of mitochondrial damage, regeneration of neurites, and cell survival in a concentration-dependent manner. Taken together, our study showed reversibility of mitochondrial morphological and functional damage in stressed neuronal cells and revealed that PGC-1α mediated mitochondrial biogenesis played a critical role in the cellular recovery. This molecular mechanism could be a target for neuroprotection and neurorescue in neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

PGC-1a mediated mitochondrial biogenesis promotes recovery and survival of neuronal cells from cellular degeneration

You,

Knoops,

Berendschot

et al. 2024

Cell Death Discov.

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show abstract

“…p-Parkin binds to the S65 site of the ubiquitin-like domain to ubiquitinate various membrane proteins on the mitochondrial surface, eventually promoting mitophagy [ 53 ]. Mitophagy dysfunction is a key mechanism in the cellular dysfunction and/or death in neurodegenerative diseases [ 54 ]. PINK1/Parkin regulates the initiation of mitophagy, which is crucial for mitochondrial quality control, potential interventions centered around their regulation of mitophagy are thought to offer new strategies for the treatment of neurodegenerative diseases [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Panax notoginseng saponins prevent dementia and oxidative stress in brains of SAMP8 mice by enhancing mitophagy

Yang,

Chen,

Lin

et al. 2024

BMC Complement Med Ther

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Background Mitochondrial dysfunction is one of the distinctive features of neurons in patients with Alzheimer’s disease (AD). Intraneuronal autophagosomes selectively phagocytose and degrade the damaged mitochondria, mitigating neuronal damage in AD. Panax notoginseng saponins (PNS) can effectively reduce oxidative stress and mitochondrial damage in the brain of animals with AD, but their exact mechanism of action is unknown. Methods Senescence-accelerated mouse prone 8 (SAMP8) mice with age-related AD were treated with PNS for 8 weeks. The effects of PNS on learning and memory abilities, cerebral oxidative stress status, and hippocampus ultrastructure of mice were observed. Moreover, changes of the PTEN-induced putative kinase 1 (PINK1)-Parkin, which regulates ubiquitin-dependent mitophagy, and the recruit of downstream autophagy receptors were investigated. Results PNS attenuated cognitive dysfunction in SAMP8 mice in the Morris water maze test. PNS also enhanced glutathione peroxidase and superoxide dismutase activities, and increased glutathione levels by 25.92% and 45.55% while inhibiting 8-hydroxydeoxyguanosine by 27.74% and the malondialdehyde production by 34.02% in the brains of SAMP8 mice. Our observation revealed the promotion of mitophagy, which was accompanied by an increase in microtubule-associated protein 1 light chain 3 (LC3) mRNA and 70.00% increase of LC3-II/I protein ratio in the brain tissues of PNS-treated mice. PNS treatment increased Parkin mRNA and protein expression by 62.80% and 43.80%, while increasing the mRNA transcription and protein expression of mitophagic receptors such as optineurin, and nuclear dot protein 52. Conclusion PNS enhanced the PINK1/Parkin pathway and facilitated mitophagy in the hippocampus, thereby preventing cerebral oxidative stress in SAMP8 mice. This may be a mechanism contributing to the cognition-improvement effect of PNS.

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The Interplay of Mitochondrial Bioenergetics and Dopamine Agonists as an Effective Disease-Modifying Therapy for Parkinson’s Disease

Neha,

Mazahir,

Khan

et al. 2024

Mol Neurobiol

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Mitochondrial dysfunction: A notable contributor to the progression of Alzheimer's and Parkinson's disease

Cited by 9 publications

References 40 publications

PGC-1a mediated mitochondrial biogenesis promotes recovery and survival of neuronal cells from cellular degeneration

PGC-1a mediated mitochondrial biogenesis promotes recovery and survival of neuronal cells from cellular degeneration

Panax notoginseng saponins prevent dementia and oxidative stress in brains of SAMP8 mice by enhancing mitophagy

The Interplay of Mitochondrial Bioenergetics and Dopamine Agonists as an Effective Disease-Modifying Therapy for Parkinson’s Disease

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