Emerging Therapeutic Approaches for Neurodegenerative Diseases

The most common neurodegenerative diseases (ND) include Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD), as well as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Protein misfolding and aggregation are the key hallmarks of these neurodegenerative diseases, which may lead to cell death, axonal regeneration failure, demyelination, and overall neuronal structural and functional deficits. Usually, ND is diagnosed at a very advanced stage and conventional therapies are directed at treating neurological symptoms but have no effect on disease progression. In general, several pathological processes contributes to misfolding proteins/protein aggregates and their postconsequences, including impairment of autophagy, microtubule destabilization, neuroinflammation, proteostasis, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress, calcium homeostasis, and neurogenesis impairment. Indeed, several signaling pathways critically linked with these pathological processes are now becoming attractive targets and investigated for their beneficial effects by restricting the progression of ND. In particular, certain signaling mechanisms and proteins found to show an integral involvement in the pathogenesis of ND and had shown promising results in preclinical and/or clinical contexts. For ex; novel autophagy stimulators, drugs acting on mTOR, NRF2, TLR, purinergic signaling; drugs acting on neuroinflammatory signaling pathways, Heat Shock Proteins (HSP), sestrins, sirtuins, some PDE-inhibitors, miRNA’s have gained a lot of attention in the therapy of ND and are included in the following discussion.

Keywords: Heat shock proteins, Neurodegenerative disorder, Neuroinflammation, Novel therapy, miRNA, mTOR, NRF2, PDE inhibitor, Protein misfolding, Purinergic, Sirtuins, TLR.