Enzymatic Targets for Drug Discovery Against Alzheimer's Disease

Effects of Carbonic Anhydrase Inhibitors on Mitochondrial Dysfunction and Consequently on Alzheimer’s Disease

Author(s): Devyani Bhatnagar, Shreya Ladhe and Dileep Kumar * .

Pp: 205-220 (16)

DOI: 10.2174/9789815136142123010012

* (Excluding Mailing and Handling)

Abstract

With the discovery of Carbonic Anhydrase (CA) and its isoenzymes in various Alzheimer’s disease (AD) models and the brain of AD patients, the role of CA in AD pathology has become of keen interest among scholars around the world. Several experiments were performed to investigate the same, albeit they didn’t provide us with the exact mechanism through which CAs are involved in AD progression, but they gave us an important insight into the beneficial outcomes of CA inhibition. Carbonic Anhydrase Inhibitor (CAI) administration showed a significant reduction in the release of the proapoptotic factor- Cytochrome C (cyt C) from the challenged mitochondria (under oxidative stress). Thus, a link between ageing, oxidative stress, mitochondria dysfunction and pathogenesis of Alzheimer’s disease was established. Treatment with CAI indirectly lowers neuronal loss and, thus, cognitive impairment, which are characteristic features of AD. Though, the precise functions of CA in exaggerating or mediating AD still remain hazy, with the support of various scholarships globally, the use of CAII (an isoenzyme of CA) as a potential biomarker for AD can be proposed.

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