title: What lysosomes actually tell us about Parkinson's disease?
abstract: Parkinson's disease is a common neurodegenerative disorder of unknown origin mainly characterized by the loss of neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta and the presence of intraneuronal proteinaceous inclusions called Lewy bodies. Lysosomes are dynamic organelles that degrade, in a controlled manner, cellular components delivered via the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways. Increasing amounts of evidence suggest a central role of lysosomal impairment in PD aetiology. This review provides an update on how genetic evidence support this connection and highlights how the neuropathologic and mechanistic evidence might relate to the disease process in sporadic forms of Parkinson's disease. Finally, we discuss the influence of ageing on lysosomal impairment and PD aetiology and therapeutic strategies targeting lysosomal function.
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bourdenx
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France. Electronic address: benjamin.dehay@u-bordeaux.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dehay
mesh_terms: D000375:Aging / Q000502:physiology*; D001343:Autophagy / Q000502:physiology; D059290:Dopaminergic Neurons / Q000378:metabolism; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D016631:Lewy Bodies / Q000502:physiology*; D008247:Lysosomes / Q000502:physiology*; D008543:Melanins / Q000378:metabolism; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013378:Substantia Nigra / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics
chemical_list: D008543:Melanins; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins; C014121:neuromelanin; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Lysosomes; Neurodegeneration; Parkinson’s disease; Therapeutic