title: Therapeutic intervention at cellular quality control systems in Alzheimer's and Parkinson's diseases.
abstract: Cellular homeostasis relies on quality control systems so that damaged biologic structures are either repaired or degraded and entirely replaced by newly formed proteins or even organelles. The clearance of dysfunctional cellular structures in long-lived postmitotic cells, like neurons, is essential to eliminate, per example, defective mitochondria, lipofuscin-loaded lysosomes and oxidized proteins. Short-lived proteins are degraded mainly by proteases and proteasomes whether most long-lived proteins and all organelles are digested by autophagy in the lysosomes. Recently, it an interplay was established between the ubiquitin-proteasome system and macroautophagy, so that both degradative mechanisms compensate for each other. In this article we describe each of these clearance systems and their contribution to neuronal quality control. We will highlight some of the findings that provide evidence for the dysfunction of these systems in Alzheimer's and Parkinson's diseases. Ultimately, we provide an outline on potential therapeutic interventions based on the modulation of cellular degradative systems.
authors: Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
authors: Daniela M
authors: DM
authors: Arduino
authors: A Raquel
authors: AR
authors: Esteves
authors: Diana F F
authors: DF
authors: Silva
authors: Diogo
authors: D
authors: Martins-Branco
authors: Daniel
authors: D
authors: Santos
authors: Diana F Gomes
authors: DF
authors: Pimentel
authors: Sandra M
authors: SM
authors: Cardoso
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D002491:Central Nervous System Agents / Q000494:pharmacology*; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy*; D059748:Proteolysis
chemical_list: D002491:Central Nervous System Agents; D008062:Lipofuscin