Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Apr 8;13(7):648.
doi: 10.3390/cells13070648.

Mitochondrial Permeability Transition, Cell Death and Neurodegeneration

Artyom Y Baev  1   2 , Andrey Y Vinokurov  3 , Elena V Potapova  3 , Andrey V Dunaev  3 , Plamena R Angelova  4 , Andrey Y Abramov  4
Affiliations
Review

Mitochondrial Permeability Transition, Cell Death and Neurodegeneration

Artyom Y Baev et al. Cells. .

Abstract

Neurodegenerative diseases are chronic conditions occurring when neurons die in specific brain regions that lead to loss of movement or cognitive functions. Despite the progress in understanding the mechanisms of this pathology, currently no cure exists to treat these types of diseases: for some of them the only help is alleviating the associated symptoms. Mitochondrial dysfunction has been shown to be involved in the pathogenesis of most the neurodegenerative disorders. The fast and transient permeability of mitochondria (the mitochondrial permeability transition, mPT) has been shown to be an initial step in the mechanism of apoptotic and necrotic cell death, which acts as a regulator of tissue regeneration for postmitotic neurons as it leads to the irreparable loss of cells and cell function. In this study, we review the role of the mitochondrial permeability transition in neuronal death in major neurodegenerative diseases, covering the inductors of mPTP opening in neurons, including the major ones-free radicals and calcium-and we discuss perspectives and difficulties in the development of a neuroprotective strategy based on the inhibition of mPTP in neurodegenerative disorders.

Keywords: astrocyte; cell death; mitochondrial permeability transition; neurodegeneration; neuron.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Previous and current PTP candidates. (A) ANT–VDAC model of PTP—partially refuted; (B) mitochondria phosphate carrier model of PTP—refuted; FOF1-ATP synthase as candidate for PTP-forming protein in its dimeric (C) and monomeric (D) forms.
Figure 2
Figure 2
Schematic representation of PTP-related pathophysiological processes during Alzheimer’s disease.
Figure 3
Figure 3
Schematic representation of PTP-related pathophysiological processes during Parkinson’s disease.
See this image and copyright information in PMC

References

    1. Spillantini M.G., Goedert M. Neurodegeneration and the ordered assembly of alpha-synuclein. Cell Tissue Res. 2018;373:137–148. doi: 10.1007/s00441-017-2706-9. - DOI - PMC - PubMed
    1. Rollo J., Crawford J., Hardy J. A dynamical systems approach for multiscale synthesis of Alzheimer’s pathogenesis. Neuron. 2023;111:2126–2139. doi: 10.1016/j.neuron.2023.04.018. - DOI - PubMed
    1. Abramov A.Y., Berezhnov A.V., Fedotova E.I., Zinchenko V.P., Dolgacheva L.P. Interaction of misfolded proteins and mitochondria in neurodegenerative disorders. Biochem. Soc. Trans. 2017;45:1025–1033. doi: 10.1042/BST20170024. - DOI - PubMed
    1. Schapira A.H. Mitochondrial diseases. Lancet. 2012;379:1825–1834. doi: 10.1016/S0140-6736(11)61305-6. - DOI - PubMed
    1. Abramov A.Y., Canevari L., Duchen M.R. Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase. J. Neurosci. Off. J. Soc. Neurosci. 2004;24:565–575. doi: 10.1523/JNEUROSCI.4042-03.2004. - DOI - PMC - PubMed

Publication types

MeSH terms