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However, two lines of evidence argue that lipofuscin may play a yet unidentified role for pathological cellular functions: (i) Genetic forms of premature accumulation of similar autofluorescent material in neuronal ceroid lipofuscinosis indicate a direct disease\u2010associated link to lipofuscin; (ii) Retinal pigment epithelium cell lipofuscin is mechanistically linked to age\u2010associated macular degeneration. Here, we purified autofluorescent material from the temporal and hippocampal cortices of three different human individuals by a two\u2010step ultracentrifugation on sucrose gradients. For human brain lipofuscin, we could identify a common set of 49 (among &gt; 200 total) proteins that are mainly derived from mitochondria, cytoskeleton, and cell membrane. This brain lipofuscin proteome was validated in an interspecies comparison with whole brain rat lipofuscin (total &gt; 300 proteins), purified by the same procedure, yielding an overlap of 32 proteins (64%) between lipofuscins of both species. Our study is the first to characterize human and rat brain lipofuscin and identifies high homology, pointing to common cellular pathomechanisms of age\u2010associated lipofuscin accumulation despite the huge (40\u2010fold) difference in the lifespan of these species. Our identification of these distinct proteins will now allow research in disturbed molecular pathways during age\u2010associated dysfunctional lysosomal degradation.<\/jats:p>","DOI":"10.1002\/pmic.201100668","type":"journal-article","created":{"date-parts":[[2012,6,18]],"date-time":"2012-06-18T04:38:34Z","timestamp":1339994314000},"page":"2445-2454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Human and rat brain lipofuscin proteome"],"prefix":"10.1002","volume":"12","author":[{"given":"Philipp","family":"Ottis","sequence":"first","affiliation":[{"name":"Department of Neuropathology Heinrich Heine University of D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Koppe","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Heinrich Heine University of D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Onisko","sequence":"additional","affiliation":[{"name":"OniPro  Kensington CA USA"},{"name":"USDA  Albany CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Dynin","sequence":"additional","affiliation":[{"name":"USDA  Albany CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Arzberger","sequence":"additional","affiliation":[{"name":"Department Neuropathology Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  M\u00fcnchen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Kretzschmar","sequence":"additional","affiliation":[{"name":"Department Neuropathology Ludwig\u2010Maximilians\u2010Universit\u00e4t M\u00fcnchen  M\u00fcnchen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus R.","family":"Requena","sequence":"additional","affiliation":[{"name":"Department of Medicine and CIMUS Biomedical Research Institute University of Santiago de Compostela\u2010IDIS  Santiago Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Silva","sequence":"additional","affiliation":[{"name":"USDA  Albany CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Huston","sequence":"additional","affiliation":[{"name":"Center for Behavioral Neuroscience Department Experimental Psychology Heinrich Heine University of D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Korth","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Heinrich Heine University of D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,20]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1","article-title":"Mikroskopiske unders\u00f6gelser af nervesystemet","volume":"10","author":"Hannover A.","year":"1842","journal-title":"Kgl. 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