Progress in the role and mechanism of TDP-43 DOI
Rongbing Li

New discovery., Год журнала: 2024, Номер unknown, С. 1 - 8

Опубликована: Сен. 20, 2024

Background: TAR DNA-binding protein 43 kDa (TDP-43) has been shown to play an important role in the development of neurodegenerative diseases, but mechanism is still under study. Methods: By utilizing “TDP43”, “disease”, and “mechanism” as keywords, 200 related studies were retrieved downloaded from Pubmed database, including 60 articles. We summarized progress understanding TDP-43 over past two years, focusing on disease systems classification upstream downstream, connection, improvement, formation. Results: TDP-43, when abnormally aggregated, phosphorylated, or mislocalized, plays a key pathological diseases. Additionally, its impact normal reproductive cell formation, development, quantity, activity, well insulin secretion activation intestinal epithelial necrosis, should not be overlooked. Mechanistically, we identified relationship between expression factors, Enterovirus D68 (EV-D68), Heterogeneous Nuclear Ribonucleoprotein D (HNRNPD AUF1), Endoplasmic Reticulum Protein 57 (ERp57), Progranulin (PGRN), downstream factors such Meiotic Recombination Spo11 (Spo11), AMP-Activated Kinase (AMPK), Double-Strand-Break Repair Rad21 Homolog (Rad21L), IκB (IKK), TDP-43. Conclusion: neurodegeneration, which, phosphorylation, EV-d68, HNRNPD.

Язык: Английский

The Regulation of TDP-43 Structure and Phase Transitions: A Review DOI

Yanqing Liu,

Jiani Xiang,

Hang Gong

и другие.

The Protein Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Язык: Английский

Процитировано

0
Phase separation of SARS-CoV-2 nucleocapsid protein with TDP-43 is dependant on C-terminus domains DOI Open Access
Michael J. Strong,

Crystal McLellan,

Brianna Kalpanis

и другие.

Опубликована: Июль 4, 2024

The SARS-CoV-2 nucleocapsid protein (N protein) is critical to viral replication by undergoing liquid-liquid phase separation seed the formation of a ribonucleoprotein (RNP) complex drive genomic RNA (gRNA) translation and in also suppressing both stress granules processing bodies which postulated increase uncoated gRNA availability. N can form biomolecular condensates with broad range host endogenous proteins including binding (RBPs). Amongst these RBPs are that associated pathological neuronal glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, TAR DNA 43 kDa (TDP-43) forms over 95% amyotrophic lateral sclerosis cases. In this study, we demonstrate TDP-43 dependant on C-terminus domain (N-CTD) intrinsically disordered TDP-43. This process markedly accelerated presence RNA. silico modelling suggests condensate formed composed quadriplex C terminus incorporated.

Язык: Английский

Процитировано

2
Promising animal models for amyotrophic lateral sclerosis drug discovery: a comprehensive update DOI Creative Commons
Léa Lescouzères, Scott B. Patten

Expert Opinion on Drug Discovery, Год журнала: 2024, Номер 19(10), С. 1213 - 1233

Опубликована: Авг. 8, 2024

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Several animal models have been generated to understand ALS pathogenesis. They provided valuable insight into mechanisms and development therapeutic strategies.

Язык: Английский

Процитировано

2
Phase Separation of SARS-CoV-2 Nucleocapsid Protein with TDP-43 Is Dependent on C-Terminus Domains DOI Open Access
Michael J. Strong,

Crystal McLellan,

Brianna Kaplanis

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8779 - 8779

Опубликована: Авг. 12, 2024

The SARS-CoV-2 nucleocapsid protein (N protein) is critical in viral replication by undergoing liquid-liquid phase separation to seed the formation of a ribonucleoprotein (RNP) complex drive genomic RNA (gRNA) translation and suppressing both stress granules processing bodies, which postulated increase uncoated gRNA availability. N can also form biomolecular condensates with broad range host endogenous proteins including binding (RBPs). Amongst these RBPs are that associated pathological, neuronal, glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, TAR DNA 43 kDa (TDP-43) forms pathological over 95% amyotrophic lateral sclerosis cases. In this study, we demonstrate TDP-43 dependent on C-terminus domain (N-CTD) intrinsically disordered TDP-43. This process markedly accelerated presence RNA. silico modeling suggests condensate composed an quadriplex C terminus incorporated.

Язык: Английский

Процитировано

2
Fluorescence lifetime-based FRET biosensors for monitoring N-terminal domain interactions of TDP-43 in living cells: A novel resource for ALS and FTD drug discovery DOI Open Access
Noah Nathan Kochen,

Marguerite Murray,

Nagamani Vunnam

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 12, 2024

Abstract TAR DNA-binding protein 43 (TDP-43) pathological aggregates are widely implicated in Alzheimer’s disease, frontotemporal dementia and amyotrophic lateral sclerosis. While therapeutic platforms targeting TDP-43 have predominantly targeted its aggregation, recent findings suggest that loss of functional dimers multimers — essential for RNA processing occur upstream aggregation is driven through disruption N-terminal domain (NTD) interactions. Here, we demonstrate these interactions targetable via cellular fluorescence lifetime-based FRET biosensors which used to screen the FDA-approved Selleck library. Our NTD-specific hit ketoconazole rescues sorbitol-induced mislocalization ameliorates induced downregulation SREBP2, a mRNA binding target with known implication ALS. In addition, improves neurite outgrowth overexpressing neuron model motor dysfunction C. elegans. Taken together, our platform represents novel approach NTD-dependent interactions, identification validates an exciting translational premise drug discovery.

Язык: Английский

Процитировано

1
Progress in the role and mechanism of TDP-43 DOI
Rongbing Li

New discovery., Год журнала: 2024, Номер unknown, С. 1 - 8

Опубликована: Сен. 20, 2024

Background: TAR DNA-binding protein 43 kDa (TDP-43) has been shown to play an important role in the development of neurodegenerative diseases, but mechanism is still under study. Methods: By utilizing “TDP43”, “disease”, and “mechanism” as keywords, 200 related studies were retrieved downloaded from Pubmed database, including 60 articles. We summarized progress understanding TDP-43 over past two years, focusing on disease systems classification upstream downstream, connection, improvement, formation. Results: TDP-43, when abnormally aggregated, phosphorylated, or mislocalized, plays a key pathological diseases. Additionally, its impact normal reproductive cell formation, development, quantity, activity, well insulin secretion activation intestinal epithelial necrosis, should not be overlooked. Mechanistically, we identified relationship between expression factors, Enterovirus D68 (EV-D68), Heterogeneous Nuclear Ribonucleoprotein D (HNRNPD AUF1), Endoplasmic Reticulum Protein 57 (ERp57), Progranulin (PGRN), downstream factors such Meiotic Recombination Spo11 (Spo11), AMP-Activated Kinase (AMPK), Double-Strand-Break Repair Rad21 Homolog (Rad21L), IκB (IKK), TDP-43. Conclusion: neurodegeneration, which, phosphorylation, EV-d68, HNRNPD.

Язык: Английский

Процитировано

0