[Frontotemporal dementia (FTD) and genetic mutations including progranulin gene].

Abstract

Research on familial frontotemporal lobar degeneration (FTLD) has led to the discovery of disease-causing genes: microtubule-associated protein tau (MAPT), progranulin (PGRN) and valosin-containing protein (VCP). TAR DNA-binding protein of 43 kDa (TDP-43) has been identified as a major component of tau-negative ubiquitin-positive inclusions in familial and sporadic FTLD and amyotrophic lateral sclerosis (ALS), which are now referred to as TDP-43 proteinopathy. Recent findings of mutations in TDP-43 gene in familial and sporadic ALS cases confirm the pathogenetic role for TDP-43 in neurodegeneration. TDP-43 proteinopathies have been classified into 4 pathological subtypes. Type 1 is characterized by numerous dystrophic neurites (DNs), Type 2 has numerous neuronal cytoplasmic inclusions (NCIs), Type 3 has NCIs and DNs and Type 4 has neuronal intranuclear inclusions (NIIs) and DNs. There is a close relationship between such pathological subtypes of TDP-43 proteinopathy and the immunoblot pattern of C-terminal fragments of accumulated TDP-43. These results parallel our earlier findings of differing C-terminal tau fragments in progressive supranuclear palsy and corticobasal degeneration, despite identical composition of tau isoforms. Taken together, these results suggest that elucidating the mechanism of C-terminal fragment origination may shed light on the pathogenesis of several neurodegenerative disorders involving TDP-43 proteinopathy and tauopathy.

• Authors: Tetsuaki Arai, Masato Hasegawa, Masugi Nishihara, Takashi Nonaka, Fuyuki Kametani, Mari Yoshida, Yoshio Hashizume, Thomas G Beach, Mitsuya Morita, Imaharu Nakano, Tatsuro Oda, Kuniaki Tsuchiya, Haruhiko Akiyama
• Journal: Rinsho shinkeigaku = Clinical neurology (Rinsho Shinkeigaku) Vol. 48 Issue 11 Pg. 990-3 (Nov 2008) ISSN: 0009-918X [Print] Japan
• PMID: 19198141 (Publication Type: Journal Article, Review)

Chemical References

• Cell Cycle Proteins
• DNA-Binding Proteins
• GRN protein, human
• Intercellular Signaling Peptides and Proteins
• MAPT protein, human
• Progranulins
• tau Proteins
• Adenosine Triphosphatases
• VCP protein, human
• Valosin Containing Protein

Topics

• Adenosine Triphosphatases (genetics)
• Amyotrophic Lateral Sclerosis (genetics)
• Cell Cycle Proteins (genetics)
• DNA-Binding Proteins (genetics)
• Dementia (classification, genetics)
• Humans
• Intercellular Signaling Peptides and Proteins (genetics)
• Intranuclear Inclusion Bodies (metabolism)
• Mutation
• Phosphorylation
• Progranulins
• Valosin Containing Protein
• tau Proteins (genetics)