Telomerase reverse transcriptase and neurodegenerative diseases

Abstract

Neurodegenerative diseases (NDs) are chronic conditions that result in progressive damage to the nervous system, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic lateral sclerosis (ALS). Age is a major risk factor for NDs. Telomere shortening is a biological marker of cellular aging, and telomerase reverse transcriptase (TERT) has been shown to slow down this process by maintaining telomere length. The blood-brain barrier (BBB) makes the brain a unique immune organ, and while the number of T cells present in the central nervous system is limited, they play an important role in NDs. Research suggests that NDs can be influenced by modulating peripheral T cell immune responses, and that TERT may play a significant role in T cell senescence and NDs. This review focuses on the current state of research on TERT in NDs and explores the potential connections between TERT, T cells, and NDs. Further studies on aging and telomeres may provide valuable insights for developing therapeutic strategies for age-related diseases.

Molecular hallmarks of ageing in amyotrophic lateral sclerosis

“…During normal ageing, the length of telomeres decreases, and rodents with short or long telomeres display inhibition or extension of lifespan, respectively [ 3 ]. Telomere shortening is thus one of the major features of ageing that is implicated in many age-related diseases [ 75 ]. Telomerase reverse transcriptase (TERT) prevents telomere shortening by maintaining telomere length [ 75 ], and whilst telomere shortening induces genomic instability and DNA damage, it is recognised as a separate hallmark of ageing [ 3 ].…”

Potential roles of telomeres and telomerase in neurodegenerative diseases

“…Lee et al detected TERT expression and activity in adult brain tissue, including the hippocampus, olfactory bulb, and subventricular region of the lateral ventricles, which may be due to the abundance of NPCs in these regions [10,11] . However, despite studies confirming that telomerase activity is restricted to stem cellcontaining regions of the brain, TERT protein has been found to be present in mature Purkinje neurons [12] , and a variety of injuries, including ischaemia-hypoxia, radiation, and glutamate-or Nmethyl-D-aspartate (NMDA)-induced excitotoxicity, can also significantly increase TERT level in rodent neurons [12,13] .…”