{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T16:03:36Z","timestamp":1793808216568,"version":"4.6.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T00:00:00Z","timestamp":1308268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:sec><jats:label\/><jats:p> <jats:italic>J. Neurochem.<\/jats:italic> (2011) <jats:bold>118<\/jats:bold>, 399\u2013406.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>G<jats:sub>M1<\/jats:sub>\u2010gangliosidosis is a fatal neurodegenerative disorder caused by deficiency of lysosomal acid \u03b2\u2010galactosidase (\u03b2\u2010gal). Accumulation of its substrate ganglioside G<jats:sub>M1<\/jats:sub> (G<jats:sub>M1<\/jats:sub>) in lysosomes and other parts of the cell leads to progressive neurodegeneration, but underlying mechanisms remain unclear. Previous studies demonstrated an essential role for interaction of G<jats:sub>M1<\/jats:sub> with tropomyosin receptor kinase (Trk) receptors in neuronal growth, survival and differentiation. In this study we demonstrate accumulation of G<jats:sub>M1<\/jats:sub> in the cell\u2010surface rafts and lysosomes of the \u03b2\u2010gal knockout (\u03b2\u2010gal\u2212\/\u2212) mouse brain association with accumulation of Trk receptors and enhancement of its downstream signaling. Immunofluorescence and subcellular fractionation analysis revealed accumulation of Trk receptors in the late endosomes\/lysosomes of the \u03b2\u2010gal\u2212\/\u2212 mouse brain and their association with ubiquitin and p62. Administration of a chemical chaperone to \u03b2\u2010gal\u2212\/\u2212 mouse expressing human mutant R201C protein resulted in a marked reduction of intracellular storage of G<jats:sub>M1<\/jats:sub> and phosphorylated Trk. These findings indicate that G<jats:sub>M1<\/jats:sub> accumulation in rafts causes activation of Trk signaling, which may participate in the pathogenesis of G<jats:sub>M1<\/jats:sub>\u2010gangliosidosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2011.07310.x","type":"journal-article","created":{"date-parts":[[2011,5,16]],"date-time":"2011-05-16T19:40:27Z","timestamp":1305574827000},"page":"399-406","source":"Crossref","is-referenced-by-count":23,"title":["Lysosomal accumulation of Trk protein in brain of G<sub>M1<\/sub>\u2010gangliosidosis mouse and its restoration by chemical 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