Telomerase Reverse Transcriptase and Neurodegenerative Diseases

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Apr 17

PMID 37063844

Authors

Xin Yu

Meng-Meng Liu

Cai-Yun Zheng

Yu-Tong Liu

Zhuo Wang

Zhan-You Wang

Affiliations

Soon will be listed here.

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.

Citing Articles

Cellular senescence in Alzheimer's disease: from physiology to pathology.

Zhu J, Wu C, Yang L Transl Neurodegener. 2024; 13(1):55.

PMID: 39568081 PMC: 11577763. DOI: 10.1186/s40035-024-00447-4.

Telomere biology and its maintenance in schizophrenia spectrum disorders: Exploring links to cognition.

Mlakar V, Akkouh I, Halff E, Srivastava D, Birkenaes V, Ueland T Schizophr Res. 2024; 272:89-95.

PMID: 39208769 PMC: 11846775. DOI: 10.1016/j.schres.2024.08.011.

lncRNA signature mediates mitochondrial permeability transition-driven necrosis in regulating the tumor immune microenvironment of cervical cancer.

Yi C, Yang J, Zhang T, Xie Z, Xiong Q, Chen D Sci Rep. 2024; 14(1):17406.

PMID: 39075098 PMC: 11286791. DOI: 10.1038/s41598-024-65990-6.

Regulation of Tert methylation alleviates food allergy via regulating the Tert-IL10 signal pathway.

Zeng H, Xu L, Liu J, Mo L, Li M, Song S Immunol Res. 2024; 72(5):1018-1029.

PMID: 39034374 DOI: 10.1007/s12026-024-09504-6.

Molecular hallmarks of ageing in amyotrophic lateral sclerosis.

Jagaraj C, Shadfar S, Kashani S, Saravanabavan S, Farzana F, Atkin J Cell Mol Life Sci. 2024; 81(1):111.

PMID: 38430277 PMC: 10908642. DOI: 10.1007/s00018-024-05164-9.

References

Jouanne M, Rault S, Voisin-Chiret A . Tau protein aggregation in Alzheimer's disease: An attractive target for the development of novel therapeutic agents. Eur J Med Chem. 2017; 139:153-167. DOI: 10.1016/j.ejmech.2017.07.070. View

Wan T, Weir E, Johnson M, Korolchuk V, Saretzki G . Increased telomerase improves motor function and alpha-synuclein pathology in a transgenic mouse model of Parkinson's disease associated with enhanced autophagy. Prog Neurobiol. 2020; 199:101953. PMC: 7938226. DOI: 10.1016/j.pneurobio.2020.101953. View

Chen Z, Zhong C . Oxidative stress in Alzheimer's disease. Neurosci Bull. 2014; 30(2):271-81. PMC: 5562667. DOI: 10.1007/s12264-013-1423-y. View

Mietelska-Porowska A, Wojda U . T Lymphocytes and Inflammatory Mediators in the Interplay between Brain and Blood in Alzheimer's Disease: Potential Pools of New Biomarkers. J Immunol Res. 2017; 2017:4626540. PMC: 5331319. DOI: 10.1155/2017/4626540. View

Svenningsson P, Westman E, Ballard C, Aarsland D . Cognitive impairment in patients with Parkinson's disease: diagnosis, biomarkers, and treatment. Lancet Neurol. 2012; 11(8):697-707. DOI: 10.1016/S1474-4422(12)70152-7. View

Flanary B, Sammons N, Nguyen C, Walker D, Streit W . Evidence that aging and amyloid promote microglial cell senescence. Rejuvenation Res. 2007; 10(1):61-74. DOI: 10.1089/rej.2006.9096. View

Yousefzadeh M, Flores R, Zhu Y, Schmiechen Z, Brooks R, Trussoni C . An aged immune system drives senescence and ageing of solid organs. Nature. 2021; 594(7861):100-105. PMC: 8684299. DOI: 10.1038/s41586-021-03547-7. View

Williams J, Manivasagam S, Smith B, Sim J, Vollmer L, Daniels B . Astrocyte-T cell crosstalk regulates region-specific neuroinflammation. Glia. 2020; 68(7):1361-1374. PMC: 7317491. DOI: 10.1002/glia.23783. View

Polydoro M, de Calignon A, Suarez-Calvet M, Sanchez L, Kay K, Nicholls S . Reversal of neurofibrillary tangles and tau-associated phenotype in the rTgTauEC model of early Alzheimer's disease. J Neurosci. 2013; 33(33):13300-11. PMC: 3742920. DOI: 10.1523/JNEUROSCI.0881-13.2013. View

10.

Roth A, Baerlocher G, Schertzer M, Chavez E, Duhrsen U, Lansdorp P . Telomere loss, senescence, and genetic instability in CD4+ T lymphocytes overexpressing hTERT. Blood. 2005; 106(1):43-50. PMC: 1895130. DOI: 10.1182/blood-2004-10-4144. View

11.

. 2016 Alzheimer's disease facts and figures. Alzheimers Dement. 2016; 12(4):459-509. DOI: 10.1016/j.jalz.2016.03.001. View

12.

Baruch-Eliyahu N, Rud V, Braiman A, Priel E . Telomerase increasing compound protects hippocampal neurons from amyloid beta toxicity by enhancing the expression of neurotrophins and plasticity related genes. Sci Rep. 2019; 9(1):18118. PMC: 6889131. DOI: 10.1038/s41598-019-54741-7. View

13.

Jackson-Lewis V, Przedborski S . Protocol for the MPTP mouse model of Parkinson's disease. Nat Protoc. 2007; 2(1):141-51. DOI: 10.1038/nprot.2006.342. View

14.

Ait-Aissa K, Kadlec A, Hockenberry J, Gutterman D, Beyer A . Telomerase reverse transcriptase protects against angiotensin II-induced microvascular endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2018; 314(5):H1053-H1060. PMC: 6008150. DOI: 10.1152/ajpheart.00472.2017. View

15.

Eitan E, Tichon A, Gazit A, Gitler D, Slavin S, Priel E . Novel telomerase-increasing compound in mouse brain delays the onset of amyotrophic lateral sclerosis. EMBO Mol Med. 2012; 4(4):313-29. PMC: 3376858. DOI: 10.1002/emmm.201200212. View

16.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View

17.

Lu W, Zhang Y, Liu D, Songyang Z, Wan M . Telomeres-structure, function, and regulation. Exp Cell Res. 2012; 319(2):133-41. PMC: 4051234. DOI: 10.1016/j.yexcr.2012.09.005. View

18.

Kowal S, Dall T, Chakrabarti R, Storm M, Jain A . The current and projected economic burden of Parkinson's disease in the United States. Mov Disord. 2013; 28(3):311-8. DOI: 10.1002/mds.25292. View

19.

Bieschke J, Zhang Q, Bosco D, Lerner R, Powers E, Wentworth Jr P . Small molecule oxidation products trigger disease-associated protein misfolding. Acc Chem Res. 2006; 39(9):611-9. DOI: 10.1021/ar0500766. View

20.

Barsov E . Telomerase and primary T cells: biology and immortalization for adoptive immunotherapy. Immunotherapy. 2011; 3(3):407-21. PMC: 3120014. DOI: 10.2217/imt.10.107. View