Emerging Roles of Signal Transduction Pathways in Neurodegenerative Diseases. Hunting New Possible Therapeutic Molecular Targets

Abstract

Illnesses following the degeneration of the nervous system can occur due to aging or genetic mutations and represent a clinical concern. In neurodegenerative diseases, loss of neuronal structure and functions mainly causes cognitive impairment, representing an increasing social burden. In neurodegenerative diseases, the progressive loss of vulnerable populations of neurons in specific regions of the central nervous system was traced to different pathological events, such as misfolded proteins’ accumulation, abnormalities in proteasomes or phagosomes, as well as anomalies in lysosomes or mitochondria. Many research efforts identified important events involved in neurodegeneration, but the complex pathogenesis of neurodegenerative diseases is far from being fully elucidated. More recently, insights into the signal transduction pathways acting in the nervous system contributed to unveiling some molecular mechanisms triggering neurodegeneration. Abnormalities in the intra- or inter-cellular signaling were described to be involved in the pathogenesis of neurodegenerative disease. Understanding the signal transduction pathways that impact the nervous system homeostasis can offer a wide panel of potential targets for modulating therapeutic approaches. The present review will discuss the main signal transduction pathways involved in neurodegenerative disorders.

DNA methylation patterns in the frontal lobe white matter of multiple system atrophy, Parkinson’s disease, and progressive supranuclear palsy: A cross-comparative investigation

“…Moreover, therapeutic models of RNAi are being extensively studied, with short hairpin (sh) RNA being the most commonly used construct in animal models of HD, AD, and PD [21]. Intra- or inter-cellular signalling mechanisms have also been described to be involved in the pathogenesis of neurodegenerative diseases with effectors and/or components of the signal transduction pathways playing important roles in progression, and possibly in the initiation, of these diseases [64]. Mechanisms relating to ER stress, mitochondrial functions and endosomal transport have been extensively reported in neurodegenerative diseases including PD, with PARK17 playing a role in the retrotransfer of proteins from endosomes in the pre-lysosomal compartment network to the trans-Golgi network, and PARK9 and ATP13A2 coding for endo-/lysosomal related proteins, HTRA2 (PARK13) being crucial to maintaining normal mitochondrial function and ERS-coupled apoptotic cell death being implicated in neurodegeneration [13, 58].…”

Multifunctional nanoparticle-mediated combining therapy for human diseases

“…NDs represent the gradual deterioration of the function and structure of the neuron populations in the central nervous system (CNS). 423 Immunocompetence reduction with age and chronic neuroinflammation are underlying causes of NDs, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). 424 Insufficient clearance of the misfolded proteins can also induce NDs.…”