Editing Multiple system atrophy (section)

==Pathophysiology==

Multiple system atrophy can be explained as cell loss and [[gliosis]] or a proliferation of [[astrocyte]]s in damaged areas of the central nervous system. This damage forms a scar which is then termed a glial scar.<ref  name=Wenning04/> The presence of [[inclusion bodies]] known as Papp–Lantos bodies, in the movement, balance, and autonomic-control centres of the brain are the defining histopathologic hallmark of MSA.<ref name="pmid20309568">{{cite journal | vauthors = Jellinger KA, Lantos PL | title = Papp-Lantos inclusions and the pathogenesis of multiple system atrophy: an update | journal = Acta Neuropathologica | volume = 119 | issue = 6 | pages = 657–667 | date = June 2010 | pmid = 20309568 | doi = 10.1007/s00401-010-0672-3 | s2cid = 19759468 }}</ref>

The major filamentous component of Papp-Lantos bodies, glial and neuronal cytoplasmic inclusions, is [[alpha-synuclein]].<ref name="pmid9829806">{{cite journal | vauthors = Arima K, Uéda K, Sunohara N, Arakawa K, Hirai S, Nakamura M, Tonozuka-Uehara H, Kawai M | display-authors = 6 | title = NACP/alpha-synuclein immunoreactivity in fibrillary components of neuronal and oligodendroglial cytoplasmic inclusions in the pontine nuclei in multiple system atrophy | journal = Acta Neuropathologica | volume = 96 | issue = 5 | pages = 439–444 | date = November 1998 | pmid = 9829806 | doi = 10.1007/s004010050917 | s2cid = 10804119 }}</ref> Mutations in this substance may play a role in the disease.<ref name="pmid19771175">{{cite journal | vauthors = Al-Chalabi A, Dürr A, Wood NW, Parkinson MH, Camuzat A, Hulot JS, Morrison KE, Renton A, Sussmuth SD, Landwehrmeyer BG, Ludolph A, Agid Y, Brice A, Leigh PN, Bensimon G | display-authors = 6 | title = Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy | journal = PLOS ONE | volume = 4 | issue = 9 | pages = e7114 | date = September 2009 | pmid = 19771175 | pmc = 2743996 | doi = 10.1371/journal.pone.0007114 | doi-access = free | bibcode = 2009PLoSO...4.7114A }}</ref> The conformation of the alpha-synuclein is different from that of alpha-synuclein in [[Lewy bodies]].<ref name="pmid29743672">{{cite journal | vauthors = Peng C, Gathagan RJ, Covell DJ, Medellin C, Stieber A, Robinson JL, Zhang B, Pitkin RM, Olufemi MF, Luk KC, Trojanowski JQ, Lee VM | display-authors = 6 | title = Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies | journal = Nature | volume = 557 | issue = 7706 | pages = 558–563 | date = May 2018 | pmid = 29743672 | pmc = 5970994 | doi = 10.1038/s41586-018-0104-4 | bibcode = 2018Natur.557..558P }}</ref> The disease probably starts with an oligodendrogliopathy.<ref>{{cite journal | vauthors = Stefanova N, Wenning GK | title = Review: Multiple system atrophy: emerging targets for interventional therapies | journal = Neuropathology and Applied Neurobiology | volume = 42 | issue = 1 | pages = 20–32 | date = February 2016 | pmid = 26785838 | pmc = 4788141 | doi = 10.1111/nan.12304 }}</ref> It has been proposed that the α-synuclein inclusions found in Oligodendrocytes result from the pruning and the engulfment of diseased axonal segments containing aggregated α-synuclein, i.e., of Lewy neurites <ref>{{cite journal | vauthors = De Nuccio F, Kashyrina M, Serinelli F, Laferrière F, Lofrumento DD, De Giorgi F, Ichas F | title = Oligodendrocytes Prune Axons Containing α-Synuclein Aggregates In Vivo: Lewy Neurites as Precursors of Glial Cytoplasmic Inclusions in Multiple System Atrophy? | journal = Biomolecules | volume = 13 | issue = 2 | pages = 269 | date = February 2023 | pmid = 36830639 | pmc = 9953613 | doi = 10.3390/biom13020269 | doi-access = free }}</ref>

[[Tau proteins]] have been found in some glial [[cytoplasmic]] inclusion bodies.<ref name="pmid11307630">{{cite journal | vauthors = Piao YS, Hayashi S, Hasegawa M, Wakabayashi K, Yamada M, Yoshimoto M, Ishikawa A, Iwatsubo T, Takahashi H | display-authors = 6 | title = Co-localization of alpha-synuclein and phosphorylated tau in neuronal and glial cytoplasmic inclusions in a patient with multiple system atrophy of long duration | journal = Acta Neuropathologica | volume = 101 | issue = 3 | pages = 285–293 | date = March 2001 | pmid = 11307630 | doi = 10.1007/s004010000292 | s2cid = 25650403 }}</ref>