Apolipoprotein D-mediated preservation of lysosomal function promotes cell survival and delays motor impairment in Niemann-Pick type A disease

The Neuroprotective Lipocalin Apolipoprotein D Stably Interacts with Specific Subtypes of Detergent-Resistant Membrane Domains in a Basigin-Independent Manner

“…After electrophoresis, proteins were transferred to PVDF membranes using standard procedures, and exposed to rabbit serum anti-hApoD (custom made by Abyntek Biopharma against purified ApoD [ 26 ]), goat serum anti-mouse ApoD (sc-34760; Santa Cruz Biotechnology), mouse anti-Basigin (MA1-19,201; Thermo Scientific), mouse anti-caveolin-1 (sc-894; Santa Cruz Biotechnology), mouse anti-Lamp2 (H4B4; DSHB), mouse anti-flotillin 1 (610,820; Becton Dickinson) or mouse anti-PMCA (sc-20028; Santa Cruz Biotechnology), followed by HRP-conjugated secondary antibodies (Santa Cruz Biotechnology). The rabbit serum anti-hApoD specificity has been validated in our previous reports [ 6 , 12 ] by comparison with other anti-hApoD sera or monoclonal antibodies. In this work, the serum was purified with gel Melon (44,600; Thermo Scientific-Pierce) and titrated through dilution series for each technique using the astrocytic (1321N1) and neuronal (SH-SY5Y) cell lines as positive and negative controls respectively.…”

“…ApoD is one of the few genes consistently upregulated in the vertebrate ageing brain [ 5 ] and in an amazingly wide array of neurodegenerative and psychiatric diseases of diverse aetiology, including Alzheimer’s disease or lysosomal storage diseases (e.g. [ 6 , 7 ]). A recent systematic review on the apparently diverse functions carried out by ApoD within and outside the nervous system [ 8 ] supports a unique biochemical role: the management of cellular and extracellular lipid structures and their redox state.…”

“…The stable presence of ApoD in lysosomes is sufficient and necessary for the recovery from oxidation-induced lysosomal membrane permeabilization [ 12 ]. This property determines the viability of cells under experimental OS [ 13 ], in pathologies hampering lysosomal function like Niemann-Pick type A disease [ 6 ] or in proteinopathies requiring optimal autophagic activity [ 14 ]. Furthermore, lysosomal ApoD is required for an adequate plasma membrane-lysosome traffic that controls the glycocalyx composition, particularly ganglioside content and distribution, with relevant functional consequences in the nervous system: Without ApoD, complete myelin compaction is halted throughout life [ 15 ].…”

The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review

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