Mitochondrial dysfunctions, oxidative stress and neuroinflammation as therapeutic targets for neurodegenerative diseases: An update on current advances and impediments

Abstract

Neurodegenerative diseases (NDs) such as Alzheimer disease (AD), Parkinson disease (PD), and Huntington disease (HD) represent a major socio-economic challenge in view of their high prevalence yet poor treatment outcomes affecting quality of life. The major challenge in drug development for these NDs is insufficient clarity about the mechanisms involved in pathogenesis and pathophysiology. Mitochondrial dysfunction, oxidative stress and inflammation are common pathways that are linked to neuronal abnormalities and initiation of these diseases. Thus, elucidating the shared initial molecular and cellular mechanisms is crucial for recognizing novel remedial targets, and developing therapeutics to impede or stop disease progression. In this context, use of multifunctional compounds at early stages of disease development unclogs new avenues as it acts on act on multiple targets in comparison to single target concept. In this review, we summarize overview of the major findings and advancements in recent years focusing on shared mechanisms for better understanding might become beneficial in searching more potent pharmacological interventions thereby reducing the onset or severity of various NDs.

Keywords: Autophagy; Mitochondrial dysfunction; Multitargeted therapeutics; Neurodegenerative diseases; Neuroinflammation; Oxidative stress.