Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits

• Published in: Brain (London, England : 1878) Vol. 134; no. 1; pp. 258 - 277
• Main Authors: Yang, Dun-Sheng, Stavrides, Philip, Mohan, Panaiyur S., Kaushik, Susmita, Kumar, Asok, Ohno, Masuo, Schmidt, Stephen D., Wesson, Daniel, Bandyopadhyay, Urmi, Jiang, Ying, Pawlik, Monika, Peterhoff, Corrinne M., Yang, Austin J., Wilson, Donald A., St George-Hyslop, Peter, Westaway, David, Mathews, Paul M., Levy, Efrat, Cuervo, Ana M., Nixon, Ralph A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.01.2011
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Analysis of Variance; Animals; Autophagy - physiology; Biological and medical sciences; Blotting, Western; Brain - metabolism; Brain - pathology; Brain - physiopathology; Conditioning (Psychology); Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Enzyme-Linked Immunosorbent Assay; Fear; Habituation, Psychophysiologic; Immunohistochemistry; Lysosomes - metabolism; Lysosomes - pathology; Medical sciences; Memory Disorders - genetics; Memory Disorders - metabolism; Memory Disorders - pathology; Memory Disorders - physiopathology; Mice; Mice, Transgenic; Neurology; Neurons - metabolism; Neurons - pathology; Original; Cystatin; Animal model; Memory disorder; Nervous system diseases; cystatin B; Cognitive disorder; autophagy; Enzyme; Alzheimer disease; Lysosome; Cerebral disorder; Peptidases; Anatomic pathology; Cathepsin; Dysfunction; Central nervous system disease; Hydrolases; Degenerative disease; Amyloid; Alzheimer's disease

Autophagy, a major degradative pathway for proteins and organelles, is essential for survival of mature neurons. Extensive autophagic-lysosomal pathology in Alzheimer's disease brain contributes to Alzheimer's disease pathogenesis, although the underlying mechanisms are not well understood...