title: Activation and alteration of lysosomes in multiple system atrophy.
abstract: Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder. Its histopathological features include glial cytoplasmic inclusions that contain α-synuclein as the main component. Recently, multiple lines of evidence have suggested a role for lysosomes in the pathogenesis of many neurodegenerative diseases. To elucidate whether lysosomes are also implicated in the pathology of MSA, we carried out an immunohistochemical study using antibodies against lysosomal proteins in the brains of patients with MSA and in control brains. A robust increase in the expression and an alteration in the morphology and distribution of lysosomal-protein-positive structures were observed in MSA brains. Double immunohistochemistry demonstrated that lysosomal markers did not colocalize mainly with glial cytoplasmic inclusions, but colocalized with a microglial marker. These immunohistochemical signatures suggest that lysosomes are activated in microglia during the disease process, and play a pivotal role in the pathology of MSA.
authors.affiliation: Department of Neurology, Gunma University Graduate School of Medicine, Gunma, Japan. makiokakoki@yahoo.co.jp
authors.forename: Kouki
authors.initials: K
authors.lastname: Makioka
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Takatama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D016022:Case-Control Studies; D002402:Cathepsin D / Q000378:metabolism*; D005260:Female; D006596:Hexosaminidases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D008247:Lysosomes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism / Q000473:pathology*; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D002402:Cathepsin D; D006596:Hexosaminidases; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C497811:LAMP2 protein, human; C533922:CTSD protein, human