CELL CYCLE RE-ENTRY AND ITS PHARMACOLOGICAL IMPLICATIONS IN NEURODEGENERATIVE DISEASES

Abstract

Neurodegenerative diseases (NDDs) are one of the most frightening medical disorders that affect the brain and the nervous system. The limited amount of understanding of the NDDs makes the treatment difficult. In the pathogenesis of many neurodegenerative diseases oxidative stress, considered to play an important role and can also induce DNA damage and later cell cycle re-entry of neuronal cells. Along with oxidative stress, endoplasmic reticulum (ER) stress affects various cellular functions, which also includes cell cycle progression. Research performed for several

years has discovered that cell cycle reentry may be abortive, causing neuronal cell death, or non- abortive, leading to DNA synthesis followed by cell death in neurodegenerative diseases.

Therefore, aberrant cell cycle reentry is probably a contributing factor in disease progression rather than a secondary phenomenon. In the brain of AD patients with mild cognitive impairment, cell cycle reentry can be seen in the early stage of the disease. In the brain of PD patients, response to various neurotoxic signals, the reentry cell cycle of post-mitotic has been observed, which leads to neuronal death. On the other hand, the primary reason for the initiation of the cell cycle in neurons and the future of dedifferentiating neurons in the pathology of HD and ALS brain is yet unclear. There is the various pharmacological drug that has been developed to reduce the pathogenesis ofseveral NDDs, but they are still not helpful in eliminating the cause of these NDDs. Thus, a major focus of neuroscience research is to examine the mechanism involved in aberrant cell cycle reentry and cell death in neurons to find potential drug targets to treat NDDs.