Molecular Genetics of Frontotemporal Dementia Elucidated by Drosophila Models—Defects in Endosomal–Lysosomal Pathway
Frontotemporal dementia (FTD) is the second most common senile neurodegenerative disease. FTD is a heterogeneous disease that can be classified into several subtypes. A mutation in CHMP2B locus (CHMP2Bintron5), which encodes a component of endosomal sorting complex required for transport-III (ESCRT-...
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doaj-f9d64dce2fc442509a42b0fb452c71c42020-11-24T21:06:13ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-06-01196171410.3390/ijms19061714ijms19061714Molecular Genetics of Frontotemporal Dementia Elucidated by Drosophila Models—Defects in Endosomal–Lysosomal PathwaySarah E. Vandal0Xiaoyue Zheng1S. Tariq Ahmad2Department of Biology, Colby College, 5720 Mayflower Hill, Waterville, ME 04901, USADepartment of Biology, Colby College, 5720 Mayflower Hill, Waterville, ME 04901, USADepartment of Biology, Colby College, 5720 Mayflower Hill, Waterville, ME 04901, USAFrontotemporal dementia (FTD) is the second most common senile neurodegenerative disease. FTD is a heterogeneous disease that can be classified into several subtypes. A mutation in CHMP2B locus (CHMP2Bintron5), which encodes a component of endosomal sorting complex required for transport-III (ESCRT-III), is associated with a rare hereditary subtype of FTD linked to chromosome 3 (FTD-3). ESCRT is involved in critical cellular processes such as multivesicular body (MVB) formation during endosomal–lysosomal pathway and autophagy. ESCRT mutants causes diverse physiological defects primarily due to accumulation of endosomes and defective MVBs resulting in misregulation of signaling pathways. Charged multivesicular body protein 2B (CHMP2B) is important for neuronal physiology which especially rely on precise regulation of protein homeostasis due to their post-mitotic status. Drosophila has proven to be an excellent model for charaterization of mechanistic underpinning of neurodegenerative disorders including FTD. In this review, current understanding of various FTD-related mutations is discussed with a focus on Drosophila models of CHMP2Bintron5-associated FTD.http://www.mdpi.com/1422-0067/19/6/1714frontotemporal dementiaendosomal-lysosomal pathwayESCRTCHMP2BCHMP2Bintron5animal modelsDrosophila |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sarah E. Vandal Xiaoyue Zheng S. Tariq Ahmad |
spellingShingle |
Sarah E. Vandal Xiaoyue Zheng S. Tariq Ahmad Molecular Genetics of Frontotemporal Dementia Elucidated by Drosophila Models—Defects in Endosomal–Lysosomal Pathway International Journal of Molecular Sciences frontotemporal dementia endosomal-lysosomal pathway ESCRT CHMP2B CHMP2Bintron5 animal models Drosophila |
author_facet |
Sarah E. Vandal Xiaoyue Zheng S. Tariq Ahmad |
author_sort |
Sarah E. Vandal |
title |
Molecular Genetics of Frontotemporal Dementia Elucidated by Drosophila Models—Defects in Endosomal–Lysosomal Pathway |
title_short |
Molecular Genetics of Frontotemporal Dementia Elucidated by Drosophila Models—Defects in Endosomal–Lysosomal Pathway |
title_full |
Molecular Genetics of Frontotemporal Dementia Elucidated by Drosophila Models—Defects in Endosomal–Lysosomal Pathway |
title_fullStr |
Molecular Genetics of Frontotemporal Dementia Elucidated by Drosophila Models—Defects in Endosomal–Lysosomal Pathway |
title_full_unstemmed |
Molecular Genetics of Frontotemporal Dementia Elucidated by Drosophila Models—Defects in Endosomal–Lysosomal Pathway |
title_sort |
molecular genetics of frontotemporal dementia elucidated by drosophila models—defects in endosomal–lysosomal pathway |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-06-01 |
description |
Frontotemporal dementia (FTD) is the second most common senile neurodegenerative disease. FTD is a heterogeneous disease that can be classified into several subtypes. A mutation in CHMP2B locus (CHMP2Bintron5), which encodes a component of endosomal sorting complex required for transport-III (ESCRT-III), is associated with a rare hereditary subtype of FTD linked to chromosome 3 (FTD-3). ESCRT is involved in critical cellular processes such as multivesicular body (MVB) formation during endosomal–lysosomal pathway and autophagy. ESCRT mutants causes diverse physiological defects primarily due to accumulation of endosomes and defective MVBs resulting in misregulation of signaling pathways. Charged multivesicular body protein 2B (CHMP2B) is important for neuronal physiology which especially rely on precise regulation of protein homeostasis due to their post-mitotic status. Drosophila has proven to be an excellent model for charaterization of mechanistic underpinning of neurodegenerative disorders including FTD. In this review, current understanding of various FTD-related mutations is discussed with a focus on Drosophila models of CHMP2Bintron5-associated FTD. |
topic |
frontotemporal dementia endosomal-lysosomal pathway ESCRT CHMP2B CHMP2Bintron5 animal models Drosophila |
url |
http://www.mdpi.com/1422-0067/19/6/1714 |
work_keys_str_mv |
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