Understanding the neuronal synapse and challenges associated with the mitochondrial dysfunction in mild cognitive impairment and Alzheimer's disease

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dc.contributor.authorVerma, Harkomal
dc.contributor.authorGangwar, Prabhakar
dc.contributor.authorYadav, Anuradha
dc.contributor.authorYadav, Bharti
dc.contributor.authorRao, Rashmi
dc.contributor.authorKaur, Sharanjot
dc.contributor.authorKumar, Puneet
dc.contributor.authorDhiman, Monisha
dc.contributor.authorTaglialatela, Giulio
dc.contributor.authorMantha, Anil Kumar
dc.date.accessioned2024-01-21T10:55:17Z
dc.date.accessioned2024-08-14T07:44:15Z
dc.date.available2024-01-21T10:55:17Z
dc.date.available2024-08-14T07:44:15Z
dc.date.issued2023-09-13T00:00:00
dc.description.abstractSynaptic mitochondria are crucial for maintaining synaptic activity due to their high energy requirements, substantial calcium (Ca2+) fluctuation, and neurotransmitter release at the synapse. To provide a continuous energy supply, neurons use special mechanisms to transport and distribute healthy mitochondria to the synapse while eliminating the damaged mitochondria from the synapse. Along the neuron, mitochondrial membrane potential (?) gradient exists and is highest in the somal region. Lower ? in the synaptic region renders mitochondria more vulnerable to oxidative stress-mediated damage. Secondly, mitochondria become susceptible to the release of cytochrome c, and mitochondrial DNA (mtDNA) is not shielded from the reactive oxygen species (ROS) by the histone proteins (unlike nuclear DNA), leading to activation of caspases and pronounced oxidative DNA base damage, which ultimately causes synaptic loss. Both synaptic mitochondrial dysfunction and synaptic failure are crucial factors responsible for Alzheimer's disease (AD). Furthermore, amyloid beta (A?) and hyper-phosphorylated Tau, the two leading players of AD, exaggerate the disease-like pathological conditions by reducing the mitochondrial trafficking, blocking the bi-directional transport at the synapse, enhancing the mitochondrial fission via activating the mitochondrial fission proteins, enhancing the swelling of mitochondria by increasing the influx of water through mitochondrial permeability transition pore (mPTP) opening, as well as reduced ATP production by blocking the activity of complex I and complex IV. Mild cognitive impairment (MCI) is also associated with decline in cognitive ability caused by synaptic degradation. This review summarizes the challenges associated with the synaptic mitochondrial dysfunction linked to AD and MCI and the role of phytochemicals in restoring the synaptic activity and rendering neuroprotection in AD. � 2023 Elsevier B.V. and Mitochondria Research Society. All rights reserved.en_US
dc.identifier.doi10.1016/j.mito.2023.09.003
dc.identifier.issn15677249
dc.identifier.urihttp://10.2.3.109/handle/32116/4392
dc.identifier.urlhttps://linkinghub.elsevier.com/retrieve/pii/S1567724923000818
dc.language.isoen_USen_US
dc.publisherElsevier B.V.en_US
dc.subjectAlzheimer's diseaseen_US
dc.subjectAmyloid betaen_US
dc.subjectDNA base damageen_US
dc.subjectFree radicalsen_US
dc.subjectHyper-phosphorylated Tauen_US
dc.subjectMitochondriaen_US
dc.subjectPhytochemicalsen_US
dc.subjectSynapseen_US
dc.titleUnderstanding the neuronal synapse and challenges associated with the mitochondrial dysfunction in mild cognitive impairment and Alzheimer's diseaseen_US
dc.title.journalMitochondrionen_US
dc.typeReviewen_US
dc.type.accesstypeClosed Accessen_US

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