Back to Search Start Over

Telomere biology disorders: time for moving towards the clinic?

Authors :
Luis F.Z. Batista
Inderjeet Dokal
Roy Parker
Source :
Trends in Molecular Medicine. 28:882-891
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

Telomere biology disorders (TBDs) are a group of rare diseases caused by mutations that impair telomere maintenance. Mutations that cause reduced levels of TERC/hTR, the telomerase RNA component, are found in most TBD patients and include loss-of-function mutations in hTR itself, in hTR-binding proteins [NOP10, NHP2, NAF1, ZCCHC8, and dyskerin (DKC1)], and in proteins required for hTR processing (PARN). These patients show diverse clinical presentations that most commonly include bone marrow failure (BMF)/aplastic anemia (AA), pulmonary fibrosis, and liver cirrhosis. There are no curative therapies for TBD patients. An understanding of hTR biogenesis, maturation, and degradation has identified pathways and pharmacological agents targeting the poly(A) polymerase PAPD5, which adds 3'-oligoadenosine tails to hTR to promote hTR degradation, and TGS1, which modifies the 5'-cap structure of hTR to enhance degradation, as possible therapeutic approaches. Critical next steps will be clinical trials to establish the effectiveness and potential side effects of these compounds in TBD patients.

Details

ISSN :
14714914
Volume :
28
Database :
OpenAIRE
Journal :
Trends in Molecular Medicine
Accession number :
edsair.doi.dedup.....52eba6d1a15b2bb2ba3998365aae78a7
Full Text :
https://doi.org/10.1016/j.molmed.2022.08.001