Title:Mitochondrial Permeability Transition Pore as a Suitable Targ e t for Neuroprotective Agents Against Alzheimer’s Disease
Volume: 16
Issue: 6
Author(s): Elena F. Shevtsova, Daria V. Vinogradova, Margarita E. Neganova, Marco Avila-Rodriguez, Ghulam Md Ashraf , George E. Barreto, Sergey O. Bachurin and Gjumrakch Aliev*
Affiliation:
- “GALLY” International Biomedical Research Consulting LLC, 7733 Louis Pasteur Drive, #330, San Antonio, TX 78229,United States
Keywords:
Alzheimer's disease, Mitochondria, Mitochondrial dysfunction, Multitarget benefits, Neurodegenerative diseases,
Neuroprotective.
Abstract: Background: A considerable amount of data suggests the age-related impairments of mitochondrial
functions in the development of sporadic forms of neurodegenerative pathologies. Mitochondria
and the phenomenon of mitochondrial permeability transition (MPT), which marks the point
of no return in cell death cascades, have special value in this regard. It is important that the vulnerability
to MPT-inducing factors is increased with aging. Simultaneously, a decrease in the calcium retention
capacity of mitochondria is developed, which leads to the disturbance of the functional activity of
neurons.
Method: The systematic investigations and web content related to the importance of MPT as the target
for the search of neuroprotective and cognitive enhancing drugs, especially with multitargeted action,
are reviewed.
Results: Here, we have highlighted some experimental data that determines the importance of mitochondria
for the search of neuroprotective drugs, and drugs with multitargeted action. We have also
discussed a number of new compounds with similar properties. Being MPT inhibitors/modulators, virtually
all the compounds described in this review have the ability to exhibit a neuroprotective effect,
interact with some other targets, providing coupled beneficial therapeutic effects such as cognitive
stimulation, anti-seizure, and antidepressant actions.
Conclusion: Inhibitors of MPT, which increases calcium retention capacity of mitochondria, are considered
as promising neuroprotective drugs able not only to halt the neurodegenerative cascade, but
also to increase the functional activity of neurons.
