The Telomerase Connection of the Brain and Its Implications for Neurodegenerative Diseases

Abstract

Telomerase, consisting of the protein subunit telomerase reverse transcriptase (TERT) and RNA component TERC, is best known for maintaining and extending human telomeres, the ends of linear chromosomes, in tissues, where it is active, such as stem cells, germline cells, lymphocytes and endothelial cells. This function is considered as canonical. However, various non-canonical functions for the protein part TERT have been discovered. There are multiple such roles which can interfere with several signaling pathways, cancer development and many other processes. One of these non-canonical functions includes shuttling of the TERT protein out of the nucleus upon increased oxidative stress into the cytoplasm and organelles such as mitochondria. Mitochondrial TERT is able to protect cells from oxidative stress, DNA damage and apoptosis although the exact mechanisms are incompletely understood. Recently, a protective role for TERT was described in brain neurons. Here TERT is able to counteract effects of toxic neurodegenerative proteins via changes in gene expression, activation of neurotrophic factors as well as activation of protein degrading pathways such as autophagy. Protein degradation processes are prominently involved in degrading toxic proteins in the brain like amyloid-β, pathological tau and α-synuclein that are responsible for various neurodegenerative diseases. These new findings can have implications for the development of novel treatment strategies for neurodegenerative diseases. The current review summarizes our knowledge on the role of the telomerase protein TERT in brain function, in particular, under the aspect of age-related neurodegenerative diseases. It also describes various strategies to increase TERT levels in the brain.

Keywords: TERT; brain; neurodegenerative diseases; telomerase; telomerase activator.