Characterisation of the Lysosomal Integral Membrane Protein Type 2 (LIMP‐2)in Murine Brain

In addition to functional characterisation of the lysosomal integral membrane protein type 2 (LIMP-2) in murine brain, this work describes the pathological state of the central nervous system (CNS) in a LIMP-2 knockout mouse. Results from this study suggest that loss of LIMP-2 leads to mistrafficking of one of its ligands, a lysosomal hydrolase β-glucocerebrosidase. Furthermore, accumulation of storage material throughout the CNS, neuropathological changes, disturbed lysosomal function and apoptosis indicate that LIMP-2 plays a critical role in the brain. Additionally, both primary neuronal culture and immunohistological data reveal α-synuclein accumulation in the absence of LIMP-2 expression, pointing to a Parkinson´s disease-like phenotype in mice. Finally, the potential use of LIMP-2 as a therapeutic target in the treatment of Parkinson´s disease is explored.


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