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Cited by 46Lysosomal Storage Disorders ResearchAlzheimer's disease research and treatmentsAutophagy in Disease and Therapy

TMEM106B aggregation in neurodegenerative diseases: linking genetics to function

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Jiao, Hai-Shan, Yuan, Peng, Yu, Jin-Tai·2023·Molecular Neurodegeneration
DOI 10.1186/s13024-023-00644-1PMC PMC10413548
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Abstract

Background: Mutations of the gene TMEM106B are risk factors for diverse neurodegenerative diseases. Previous understanding of the underlying mechanism focused on the impairment of lysosome biogenesis caused by TMEM106B loss-of-function. However, mutations in TMEM106B increase its expression level, thus the molecular process linking these mutations to the apparent disruption in TMEM106B function remains mysterious. Main body: Recent new studies reported that TMEM106B proteins form intracellular amyloid filaments which universally exist in various neurodegenerative diseases, sometimes being the dominant form of protein aggregation. In light of these new findings, in this review we systematically examined previous efforts in understanding the function of TMEM106B in physiological and pathological conditions. We propose that TMEM106B aggregations could recruit normal TMEM106B proteins and interfere with their function. Conclusions: TMEM106B mutations could lead to lysosome dysfunction by promoting the aggregation of TMEM106B and reducing these aggregations may restore lysosomal function, providing a potential therapeutic target for various neurodegenerative diseases.

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  • This led to the identification of some of the earliest disease-associated genes, including APP, PS1 and PS2 in AD, SNCA and LRRK2 in PD and MAPT and GRN in FTD.

    “This subsequently led to the identification of some of the earliest disease-associated genes, including APP, PS1 and PS2 in AD, SNCA and LRRK2 in PD and MAPT and GRN in FTD.79–87”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [81]

    The section ‘Other risk factors interact with TMEM106B pathology’ says GRN loss-of-function mutations cause familial FTD, and the figure caption identifies MAPT mutations as a cause of familial frontotemporal dementia and parkinsonism (no page numbers supplied). Our copy does not substantiate the listed AD or PD genes or the claim that these were among the earliest disease-associated genes identified. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Jiao, H.-S., Yuan, P., & Yu, J.-T.
Affiliations
  • Fudan University (CN)
  • Shanghai Medical College of Fudan University (CN)
Corresponding author
  • Yuan, Peng
  • Yu, Jin-Tai
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2023-08-10
Volume
18
Issue
1
Pages
54-54
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/s13024-023-00644-1
PMC
PMC10413548
OpenAlex
W4385723500
Cited by
46
References
4
Citations by year
2026: 9 · 2025: 16 · 2024: 19 · 2023: 2
FWCI
1.64
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82271471)
  • Shanghai Municipal Science and Technology Major Project (2018SHZDZX01)
Topics
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
TMEM106B, protein aggregation, amyloid filaments, neurodegenerative diseases, lysosomal dysfunction, lysosomal biogenesis, loss-of-function mutations, gain-of-function mutations, protein recruitment, therapeutic target
MeSH terms
Humans, Membrane Proteins, Mutation, Nerve Tissue Proteins, Neurodegenerative Diseases

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