VDAC-Targeted Drugs Affecting Cytoprotection and Mitochondrial Physiology in Cerebrovascular and Cardiovascular Diseases

Author(s): Andonis Karachitos, Joaquin Jordan, Hanna Kmita*.

Journal Name: Current Medicinal Chemistry

Volume 24 , Issue 40 , 2017

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Abstract:

Background: Cerebrovascular and cardiovascular diseases are caused by impairment of the brain and/or heart circulation. Insufficient blood flow results in decreased oxygen delivery (ischemia), which affects mitochondrial functioning and consequently leads to insufficient ATP production. The predominant mitochondrial outer membrane protein, the voltagedependent anion selective channel (VDAC), is considered to be crucial for mitochondrial functioning. In human mitochondria, as in other vertebrates, three isoforms of VDAC (VDAC1-VDAC3) are present, and they likely play different roles.

Objective: In this review, we summarize the available data concerning VDAC involvement in cardiovascular and cerebrovascular diseases with regard to VDAC isoforms and discuss the use of possible VDAC-related intervention targets as well as known VDAC-interacting and cytoprotection- conferring molecules in the treatment of cerebrovascular and cardiovascular diseases.

Method and Results: The suitable references on disorders defined as cerebrovascular and cardiovascular diseases as well as VDAC contribution to these conditions were searched using PubMed and ClinicalTrials.gov databases. The review is based on the 138 carefully selected articles.

Conclusion: Mitochondrial dysfunction triggered by changes in VDAC properties undoubtedly contributes to cell death and related diseases, including cerebrovascular and cardiovascular diseases. Thus, beside diagnostic application, modulation of VDAC activity, including its isoforms, is thus of great importance for the development of efficient therapeutic interventions. Moreover, identification of VDAC-interacting molecules that protect against mitochondrial dysfunction and cell death seems to be of great importance.

Keywords: VDAC-targeted drugs, cytoprotection, mitochondrial, cerebrovascular, cardiovascular diseases, ischemia ATP.

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Article Details

VOLUME: 24
ISSUE: 40
Year: 2017
Page: [4419 - 4434]
Pages: 16
DOI: 10.2174/0929867324666170530073238
Price: $58

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