Feb 10, 2009

Endoplasmic reticulum protein quality control in neurodegenerative disease: the good, the bad and the therapy

Current Medicinal Chemistry
Wiep Scheper, Jeroen J M Hoozemans

Abstract

Neurodegenerative disorders are often characterized by the aggregation and accumulation of misfolded proteins (e.g. Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis). Aggregated proteins are very toxic to cells in culture and both in vitro and in vivo there is overwhelming evidence that these aberrant proteins are key players in neurodegeneration. Protein quality control is a cellular defense mechanism against misfolded proteins that prevents aggregate formation under physiological conditions. The presence of accumulated aggregates of misfolded proteins in many neurodegenerative disorders, suggests that protein quality control failed to restore homeostasis in these pathological conditions. In fact, evidence from observations in cellular disease models, mouse models, as well as from post mortem patient material indicates activation of the quality control machinery in response to the pathological process. In addition, interference with protein quality control by genetic or chemical manipulation often results in aggregate formation and neurodegeneration. This stresses the importance of proper quality control in neurodegenerative disorders and indicates that it may provide a target for therapeutic interventio...Continue Reading

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Mentioned in this Paper

Aggregation
Gene Products, Protein
Degenerative Diseases, Spinal Cord
Neurodegenerative Disorders Pathway
Nerve Degeneration
Oxidative Stress
Alzheimer's Disease
Amyotrophic Lateral Sclerosis
Parkinson Disease
Pathology

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