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Telomerase in Brain and its Implications in Neurodegenerative Diseases

Gabriele Saretzki

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Abstract

Telomerase is an enzyme that extends and preserves telomeres, which are the ends of chromosomes. This reverse transcriptase function is critical for dividing cells that continuously shorten their telomeres. In addition to its canonical role in maintaining telomeres in dividing cells a number of TERT (Telomerase Reverse Transcriptase)-related non-canonical functions has been described. Importantly, the RNA component of telomerase, TERC, is downregulated early in development in human brain, resulting in the loss of telomerase activity in most brain cells except neural stem cells. In contrast, the presence of the telomerase protein TERT persists during lifetime in neurons of the human brain. This makes TERT the prominent telomerase subunit in the brain and is responsible for various protective mechanisms associated with improved stress responses and increased degradation of toxic proteins. The present review highlights some new findings for telomerase in brain and its possible implications for neurodegenerative diseases and potential novel treatment strategies.

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What this paper is about

Telomerase is an enzyme that extends and preserves telomeres, which are the ends of chromosomes. This reverse transcriptase function is critical for dividing cells that continuously shorten their telomeres. In addition to its canonical role in maintaining telomeres in dividing cells a number of TERT (Telomerase Reverse Transcriptase)-related non-canonical functions has been described. Importantly, the RNA component of telomerase, TERC, is downregulated early in development in human brain, resulting in the loss of telomerase activity in most brain cells except neural stem cells. In contrast, the presence of the telomerase protein TERT persists during lifetime in neurons of the human brain. This makes TERT the prominent telomerase subunit in the brain and is responsible for various protective mechanisms associated with improved stress responses and increased degradation of toxic proteins. The present review highlights some new findings for telomerase in brain and its possible implications for neurodegenerative diseases and potential novel treatment strategies.

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Available abstract

Telomerase is an enzyme that extends and preserves telomeres, which are the ends of chromosomes. This reverse transcriptase function is critical for dividing cells that continuously shorten their telomeres. In addition to its canonical role in maintaining telomeres in dividing cells a number of TERT (Telomerase Reverse Transcriptase)-related non-canonical functions has been described. Importantly, the RNA component of telomerase, TERC, is downregulated early in development in human brain, resulting in the loss of telomerase activity in most brain cells except neural stem cells. In contrast, the presence of the telomerase protein TERT persists during lifetime in neurons of the human brain. This makes TERT the prominent telomerase subunit in the brain and is responsible for various protective mechanisms associated with improved stress responses and increased degradation of toxic proteins. The present review highlights some new findings for telomerase in brain and its possible implications for neurodegenerative diseases and potential novel treatment strategies.

Key concepts: Telomerase, Telomere, Telomerase reverse transcriptase, Telomerase RNA component, Protein subunit, Biology, Reverse transcriptase, Cell biology

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