Abstract
Telomerase is best known for its canonical function in telomere maintenance. However, a growing number of non-telomeric functions have been described. Several groups have found the telomerase protein TERT to persist in adult brain neurons. A protective role for the telomerase protein TERT had been demonstrated in cultivated mouse neurons during brain development, against excitotoxic stresses from N-methyl-D-aspartate (NMDA) and glutamate and agents known to be involved in neurodegenerative diseases such as beta amyloid peptides and hyperphosphorylated tau. In contrast, lack of telomerase and TERT protein increase oxidative stress and decrease neuronal survival. Research on telomerase and TERT protein in human neurodegenerative diseases is a relatively new field. However, there is emerging evidence of a beneficial role of telomerase in human brains and animal models of neurodegenerative diseases that suggests to explore the possibility of using telomerase activators as neuroprotective agents to combat brain ageing and to ameliorate neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. The current mini-review summarises the knowledge about this developing novel area of brain research.
Highlights
Telomerase is a reverse transcriptase best known as the enzyme that extends and maintains telomeres, the protective ends of linear chromosomes, in dividing cells
We found that only neurons, but not astrocytes expressed any TERT protein while there was some expression in human microglia, presumably due to their nature being macrophages[38]
Our findings together with that of Iannilli et al.[37] suggest that TERT protein enters neuronal mitochondria from the cytoplasm due to increased oxidative stress where it might exert a protective function. This suggestion is supported by our results of a lack of co-localisation of hyperphosphorylated tau protein and TERT protein in human hippocampi of advanced Braak stages in Alzheimer’s disease (AD) brains where we found a mutual exclusion of both proteins: neurons expressing TERT did not show any tau pathology while cells with neuropil threads or neurofibrillary tangles did not show any TERT expression[38]
Summary
Telomerase is a reverse transcriptase best known as the enzyme that extends and maintains telomeres, the protective ends of linear chromosomes, in dividing cells. The protective role of mammalian TERT in mitochondria has recently been demonstrated even in yeast where it increased the resistance against oxidative stress without interacting with telomeres or the yeast TERT which lacks the mitochondrial localisation signal[30].
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