Potential of Therapeutic Small Molecules in Apoptosis Regulation in the Treatment of Neurodegenerative Diseases: An Updated Review

Abstract

Neurodegenerative disorders (NDs) include Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) and the common feature of NDs is the progressive death of specific neurons in the brain. Apoptosis is very important in developing the nervous system, nonetheless an elevated level of cell death has been observed in the case of NDs. NDs are different in terms of their neuronal vulnerability and clinical manifestations, however they have some overlapping neurodegenerative pathways. It has been demonstrated by several studies with cell lines and animal models that apoptosis has a significant contribution to make in advancing AD, ALS, HD, and PD. Numerous dying neurons were also identified in the brains of individuals with NDs and these conditions were found to be linked with substantial cell loss along with common characteristics of apoptosis including activation of caspases and cysteine-proteases, DNA fragmentation, and chromatin condensation. It has been demonstrated that several therapeutic agents including antioxidants, minocycline, GAPDH ligands, p53 inhibitors, JNK (c-Jun N-Terminal Kinase) inhibitors, glycogen synthase kinase-3 inhibitor, non-steroidal anti-inflammatory drugs, D2 dopamine receptor agonists, FK506, cell cycle inhibitors, statins, drugs targeting peroxisome proliferator-activated receptors, and gene therapy have the potential to provide protection to neurons against apoptosis. Therefore, the use of these potential therapeutic agents might be beneficial in the treatment of NDs. In this review, we have summarized the pathways that are linked with apoptotic neuronal death in the case of various NDs. We have particularly focused on the therapeutic agents that have neuroprotective properties and the potential to regulate apoptosis in NDs.