- Open Access
Autophagy impairment: a crossroad between neurodegeneration and tauopathies
© Nassif and Hetz; licensee BioMed Central Ltd. 2012
- Received: 11 September 2012
- Accepted: 14 September 2012
- Published: 21 September 2012
Most neurodegenerative diseases involve the accumulation of misfolded proteins in the nervous system. Impairment of protein degradation pathways such as autophagy is emerging as a consistent and transversal pathological phenomenon in neurodegenerative diseases, including Alzheimer's, Huntington's, and Parkinson's disease. Genetic inactivation of autophagy in mice has demonstrated a key role of the pathway in maintaining protein homeostasis in the brain, triggering massive neuronal loss and the accumulation of abnormal protein inclusions. However, the mechanism underlying neurodegeneration due to autophagy impairment remains elusive. A paper in Molecular Neurodegeneration from Abeliovich's group now suggests a role for phosphorylation of Tau and the activation of glycogen synthase kinase 3β (GSK3β) in driving neurodegeneration in autophagy-deficient neurons. We discuss the implications of this study for understanding the factors driving neurofibrillary tangle formation in Alzheimer's disease and tauopathies.
See research article http://www.molecularneurodegeneration.com/content/7/1/48
- Amyotrophic Lateral Sclerosis
- Protein Homeostasis
- Autophagy Impairment
- Protein Misfolding Disorder
We received support from Alzheimer's Association, FONDECYT 1100176, FONDAP 15010006, ACT1109, Instituto Milenio P09-015-F. In addition we received support from the Michael J Fox Foundation for Parkinson Research, the Muscular Dystrophy Association, and the ALS Therapy Alliance.
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