Cargando…

The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics

Frontotemporal dementia (FTD) is a common cause of presenile dementia and is characterized by behavioural and/or language changes and progressive cognitive deficits. Genetics is an important component in the aetiology of FTD, with positive family history of dementia reported for 40% of cases. This r...

Descripción completa

Detalles Bibliográficos
Autores principales: Lok, Hiu Chuen, Kwok, John B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961524/
https://www.ncbi.nlm.nih.gov/pubmed/33802612
http://dx.doi.org/10.3390/ijms22052541
_version_ 1783665279224512512
author Lok, Hiu Chuen
Kwok, John B.
author_facet Lok, Hiu Chuen
Kwok, John B.
author_sort Lok, Hiu Chuen
collection PubMed
description Frontotemporal dementia (FTD) is a common cause of presenile dementia and is characterized by behavioural and/or language changes and progressive cognitive deficits. Genetics is an important component in the aetiology of FTD, with positive family history of dementia reported for 40% of cases. This review synthesizes current knowledge of the known major FTD genes, including C9orf72 (chromosome 9 open reading frame 72), MAPT (microtubule-associated protein tau) and GRN (granulin), and their impact on neuronal and glial pathology. Further, evidence for white matter dysfunction in the aetiology of FTD and the clinical, neuroimaging and genetic overlap between FTD and leukodystrophy/leukoencephalopathy are discussed. The review highlights the role of common variants and mutations in genes such as CSF1R (colony-stimulating factor 1 receptor), CYP27A1 (cytochrome P450 family 27 subfamily A member 1), TREM2 (triggering receptor expressed on myeloid cells 2) and TMEM106B (transmembrane protein 106B) that play an integral role in microglia and oligodendrocyte function. Finally, pharmacological and non-pharmacological approaches for enhancing remyelination are discussed in terms of future treatments of FTD.
format Online
Article
Text
id pubmed-7961524
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79615242021-03-17 The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics Lok, Hiu Chuen Kwok, John B. Int J Mol Sci Review Frontotemporal dementia (FTD) is a common cause of presenile dementia and is characterized by behavioural and/or language changes and progressive cognitive deficits. Genetics is an important component in the aetiology of FTD, with positive family history of dementia reported for 40% of cases. This review synthesizes current knowledge of the known major FTD genes, including C9orf72 (chromosome 9 open reading frame 72), MAPT (microtubule-associated protein tau) and GRN (granulin), and their impact on neuronal and glial pathology. Further, evidence for white matter dysfunction in the aetiology of FTD and the clinical, neuroimaging and genetic overlap between FTD and leukodystrophy/leukoencephalopathy are discussed. The review highlights the role of common variants and mutations in genes such as CSF1R (colony-stimulating factor 1 receptor), CYP27A1 (cytochrome P450 family 27 subfamily A member 1), TREM2 (triggering receptor expressed on myeloid cells 2) and TMEM106B (transmembrane protein 106B) that play an integral role in microglia and oligodendrocyte function. Finally, pharmacological and non-pharmacological approaches for enhancing remyelination are discussed in terms of future treatments of FTD. MDPI 2021-03-03 /pmc/articles/PMC7961524/ /pubmed/33802612 http://dx.doi.org/10.3390/ijms22052541 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Lok, Hiu Chuen
Kwok, John B.
The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics
title The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics
title_full The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics
title_fullStr The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics
title_full_unstemmed The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics
title_short The Role of White Matter Dysfunction and Leukoencephalopathy/Leukodystrophy Genes in the Aetiology of Frontotemporal Dementias: Implications for Novel Approaches to Therapeutics
title_sort role of white matter dysfunction and leukoencephalopathy/leukodystrophy genes in the aetiology of frontotemporal dementias: implications for novel approaches to therapeutics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961524/
https://www.ncbi.nlm.nih.gov/pubmed/33802612
http://dx.doi.org/10.3390/ijms22052541
work_keys_str_mv AT lokhiuchuen theroleofwhitematterdysfunctionandleukoencephalopathyleukodystrophygenesintheaetiologyoffrontotemporaldementiasimplicationsfornovelapproachestotherapeutics
AT kwokjohnb theroleofwhitematterdysfunctionandleukoencephalopathyleukodystrophygenesintheaetiologyoffrontotemporaldementiasimplicationsfornovelapproachestotherapeutics
AT lokhiuchuen roleofwhitematterdysfunctionandleukoencephalopathyleukodystrophygenesintheaetiologyoffrontotemporaldementiasimplicationsfornovelapproachestotherapeutics
AT kwokjohnb roleofwhitematterdysfunctionandleukoencephalopathyleukodystrophygenesintheaetiologyoffrontotemporaldementiasimplicationsfornovelapproachestotherapeutics