Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5739167 | Progress in Neurobiology | 2017 | 23 Pages |
Abstract
Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative diseases that generate important health-related direct and indirect socio-economic costs. They are characterized by severe neuronal losses in several disease-specific brain regions associated with deposits of aggregated proteins. In Alzheimer's disease, β-amyloid peptide-containing plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated microtubule-associated protein tau are the two main neuropathological lesions, while Parkinson's disease is defined by the presence of Lewy Bodies that are intraneuronal proteinaceous cytoplasmic inclusions. α-Synuclein has been identified as a major protein component of Lewy Bodies and heavily implicated in the pathogenesis of Parkinson's disease. In the past few years, evidence has emerged to explain how these aggregate-prone proteins can undergo spontaneous self-aggregation, propagate from cell to cell, and mediate neurotoxicity. Current research now indicates that oligomeric forms are probably the toxic species. This article discusses recent progress in the understanding of the pathogenesis of these diseases, with a focus on the underlying mechanisms of protein aggregation, and emphasizes the pathophysiological molecular mechanisms leading to cellular toxicity. Finally, we present the putative direct link between β-amyloid peptide and tau in causing toxicity in Alzheimer's disease as well as α-synuclein in Parkinson's disease, along with some of the most promising therapeutic strategies currently in development for those incurable neurodegenerative disorders.
Keywords
AβAPPα-SynQOLMEF2DPSPcdk5AAVAICDMAMMSASNAREDLBEGCGAPAf-1NFTsGSK3βNMDARsLRPMyocyte enhancer factor 2DCMATFEBPHFPrPscGCaseBCL2-associated agonist of cell deathBCL2-Associated XQuality of lifeChaperone-mediated autophagyBACROSSNpcα-synucleinMultiple system atrophyALPinsulin degrading enzymeIDELoadBaxBADLewy bodiesAlzheimer's diseaseParkinson's diseaseprotein aggregationTransgenicsubstantia nigra pars compactaNeurodegenerationTUNELTherapeuticPaired helical filamentsfrontotemporal dementia with Parkinsonism linked to chromosome 17DLB, Dementia with Lewy bodiesubiquitin–proteasome systemcyclin-dependent kinase 5endoplasmic reticulumsenile plaquesTranscription factor EBLewy neuritesProgressive supranuclear palsyABADLAMPCSFCerebrospinal fluidneurofibrillary tanglesAdeno-associated virusSpreadingLysosome-associated membrane proteinLDL receptor-related proteinamyloid precursor proteinBeta-amyloid peptidebacterial artificial chromosomeglucocerebrosidaseGlycogen Synthase Kinase 3-betaReactive oxygen speciessoluble N-ethylmaleimide-sensitive factor attachment protein receptorUPS
Related Topics
Life Sciences
Neuroscience
Neuroscience (General)
Authors
Mathieu Bourdenx, Nikolaos Stavros Koulakiotis, Despina Sanoudou, Erwan Bezard, Benjamin Dehay, Anthony Tsarbopoulos,