Targeting Brain-Derived Neurotrophic Factor (BDNF) - An Important Strategy to Alzheimer's Disease

Author:

Hemant S. Kanhere1,Pallavi C. Bansinge1,Helen Ratna Monica J.2,Sawan K. Rathod1

Affiliation:

1. Division of Neuroscience, Department of Pharmacology, Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur – 441 002, MS, India.

2. Post Graduate and Research Department of Chemistry, The American College, Madurai - 625 002, Tamilnadu, India.

Abstract

Many theories have been proposed to explain why candidate disease-modifying drugs (DMTs) for Alzheimer's disease (AD) failed. Late initiation of treatments during AD development, inappropriate drug dosages, incorrect selection of main therapeutic targets, and primarily inadequate understanding of the complex pathophysiology of AD are the most prominent ones. Reduced expression of Brain Derived Neurotrophic Factor (BDNF) is essential in the pathogenesis of Alzheimer's disease. BDNF plays important functions in cell survival and differentiation, neuronal outgrowth and plasticity. It can be a novel target for the treatment of the disease. In Alzheimer's disease, the hippocampus, parietal, entorhinal, and frontal cortex all have the most extreme BDNF deficits. Lower levels of BDNF can be linked to neuronal death, masking any gene-related effects. High BDNF levels have been attributed to a lower risk of dementia and Alzheimer's. Improvements in BDNF levels imparted by exercise, plant based drugs, trkB receptor agonist and BDNF enhancer drug have been proved to enhance cognitive performance. Plant-based products and nutraceuticals can boost BDNF levels. Polyphenols are essential plant compounds with a wide range of therapeutic potentials. Flavonoids like calycosin, genistein, isorhamnetin, and luteolin have been shown to affect the level of BDNF. Curcumin, a compound derived from spice turmeric (curcuma longa), has a variety of biological functions in the brain, including antidepressant properties which also increase BDNF level in the hippocampus. Riluzole is used to treat amyotrophic lateral sclerosis (ALS). In a depression model with chronic corticosteroid intake, riluzole also restores hippocampal BDNF levels. Evidence indicates that BDNF deficiency plays a role in the pathogenesis of Alzheimer's disease. Drugs used to treat Alzheimer's disease have the unintended property of modulating BDNF levels in brain regions specifically involved in the disease's pathophysiology. The discovery of molecules that precisely control BDNF in particular cellular phenotypes could increase the effectiveness of therapy against AD.

Publisher

JACS Directory

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