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.
