BENZAMIDE DERIVATIVES: A MULTIFACETED APPROACH TO TARGETING ALZHEIMER'S DISEASE PATHOLOGY

Mohammed Sahad P.*, Amirashirin K. T., Amna Hameed Thayyil, Mridhul Mohan P. and E. Tamil Jothi

ABSTRACT

Alzheimer's disease (AD) remains a prominent neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and behavioral changes. Pathologically, AD is marked by the presence of beta-amyloid plaques and neurofibrillary tangles in the brain, leading to synaptic and neuronal loss. Various hypotheses have been proposed to elucidate the underlying mechanisms of AD, including the Tau Hypothesis, Cholinergic Hypothesis, Amyloid Cascade Hypothesis, Mitochondrial Cascade Hypothesis, and Inflammation Hypothesis. These hypotheses provide insights into different aspects of AD pathology, ranging from protein aggregation to neurotransmitter dysregulation and inflammatory processes. In the search for effective treatments, numerous drug targets have been identified, including Aβ and Tau proteins, enzymes involved in Aβ production (BACE-1, γ-secretase), cholinergic pathways, serotonin receptors, and neuro-inflammatory pathways. Despite significant research efforts, developing effective therapies for AD remains challenging. Benzamide derivatives have emerged as potential candidates for AD treatment, with studies exploring their role as cholinesterase inhibitors, modulators of Aβ biosynthesis enzymes, inhibitors of tau aggregation, and antioxidants. These compounds offer a multifaceted approach to addressing different aspects of AD pathology, including enhancing cholinergic neurotransmission, reducing Aβ production, and mitigating oxidative stress and neuroinflammation. In conclusion, understanding the complex pathophysiology of AD and exploring novel therapeutic strategies, such as benzamide derivatives, holds promise for the development of effective treatments to alleviate the burden of this devastating disease. Further research is needed to fully elucidate the efficacy and safety of these compounds in clinical settings.

Keywords: Alzheimer's disease (AD), Amyloid-beta peptide (A?), Tau Protein, Benzamide derivatives, Drug Targeting.