Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Central Nervous System (CNS)
Neurodegeneration
Sensory system
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Mood Disorders
Other disorders
Muscular system
Joints
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Cross-disciplinary subjects
SFN2024: Meet our team in Chicago on booth #876 Authors
B. Ravikumar, A. Acevedo-Arozena, S. Imarisio, Z. Berger, C. Vacher et al.
Lab
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Journal
Nature Genetics
Abstract
Mutations that affect the dynein motor machinery are sufficient to cause motor neuron disease. It is not known why there are aggregates or inclusions in affected tissues in mice with such mutations and in most forms of human motor neuron disease. Here we identify a new mechanism of inclusion formation by showing that decreased dynein function impairs autophagic clearance of aggregate-prone proteins. We show that mutations of the dynein machinery enhanced the toxicity of the mutation that causes Huntington disease in fly and mouse models. Furthermore, loss of dynein function resulted in premature aggregate formation by mutant huntingtin and increased levels of the autophagosome marker LC3-II in both cell culture and mouse models, compatible with impaired autophagosome-lysosome fusion.
BIOSEB Instruments Used:
Grip strength test (BIO-GS3)
