Neuronal Deletion of Tumor Susceptibility Gene 101 (Tsg101) Causes Rapid Apoptotic Loss of Hippocampal CA3 Neurons DOI Creative Commons

Will P. Walker,

Megan Lea Ratz-Mitchem,

Kay‐Uwe Wagner

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(6), P. 786 - 786

Published: May 28, 2025

Endosomal dysfunction is one of the earliest cellular signs in Alzheimer’s disease. Tumor susceptibility gene 101 protein (TSG101) a component endosomal sorting complex required for transport (ESCRT)-I, which plays key role ubiquitinated cell surface proteins and lipids onto intraluminal vesicles multivesicular bodies trafficking to lysosomes or autophagosomes degradation, plasma membrane exosomal secretion. TSG101-dependent has been implicated propagation spread misfolded associated with neurodegenerative diseases. We used transgenesis mice study vivo consequences disrupting adult neurons. Mice lacking Tsg101 forebrain neurons (Tsg101ck2-null) showed rapid loss hippocampal progressive atrophy. Astrogliosis was apparent dentate gyrus within 1 week deleting Tsg101, followed by apoptosis CA3 accumulation autophagy adapter P62/SQSTM1 proteins. Failure detect lipidated LC3 indicated impaired rather than upregulated. markers (RAB5 RAB7) amyloid also accumulated Tsg101ck2-null mice. Our data establish critical TSG101 neuronal survival demonstrate importance assessment functions.

Language: Английский

Neuronal Deletion of Tumor Susceptibility Gene 101 (Tsg101) Causes Rapid Apoptotic Loss of Hippocampal CA3 Neurons DOI Creative Commons

Will P. Walker,

Megan Lea Ratz-Mitchem,

Kay‐Uwe Wagner

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(6), P. 786 - 786

Published: May 28, 2025

Endosomal dysfunction is one of the earliest cellular signs in Alzheimer’s disease. Tumor susceptibility gene 101 protein (TSG101) a component endosomal sorting complex required for transport (ESCRT)-I, which plays key role ubiquitinated cell surface proteins and lipids onto intraluminal vesicles multivesicular bodies trafficking to lysosomes or autophagosomes degradation, plasma membrane exosomal secretion. TSG101-dependent has been implicated propagation spread misfolded associated with neurodegenerative diseases. We used transgenesis mice study vivo consequences disrupting adult neurons. Mice lacking Tsg101 forebrain neurons (Tsg101ck2-null) showed rapid loss hippocampal progressive atrophy. Astrogliosis was apparent dentate gyrus within 1 week deleting Tsg101, followed by apoptosis CA3 accumulation autophagy adapter P62/SQSTM1 proteins. Failure detect lipidated LC3 indicated impaired rather than upregulated. markers (RAB5 RAB7) amyloid also accumulated Tsg101ck2-null mice. Our data establish critical TSG101 neuronal survival demonstrate importance assessment functions.

Language: Английский

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