Glucocerebrosidase regulators SCARB2 and TFEB are up-regulated in Lewy body disease brain

Laia Pérez-Roca, Patricia Prada-Dacasa, Cristina Segú-Vergés, Ana Gámez-Valero, María A. Serrano-Muñoz, Cristina Santos, Katrin Beyer

    Research output: Contribution to journalArticleResearch

    Abstract

    © 2019 Elsevier B.V. Mutations in the glucocerebrosidase (GCase) gene (GBA) and GCase deficiency are major risk factors for Lewy body diseases. Decreased GCase activity enhances alpha-synuclein aggregation and disease development. Lysosomal integral membrane protein type 2, encoded by SCARB2, binds GCase targeting it to lysosomes and transcription factor EB (Tfeb) regulates lysosomal proteostasis. Our aim was to find out if GCase deficiency in Lewy body diseases is accompanied by SCARB2 and TFEB deregulation at the transcriptional level involving alternative splicing as well. Relative mRNA expression of two SCARB2 and two TFEB transcripts was studied by real-time PCR in post-mortem brain samples of cases with pure Lewy body pathology (LBP), cases with concomitant LBP and Alzheimer disease-like pathology, and controls. TFEB expression was increased in the temporal cortex and caudate nucleus of LBP cases, and SCARB2 was differentially expressed. Female-gender associated overexpression of all transcripts was found in the caudate nucleus, and disease duration associated TFEB expression changes in the temporal cortex. SCARB2 and TFEB expression correlated negatively with GBA mRNA expression in the temporal cortex. Our findings show disease-specific deregulation of TFEB and SCARB2 expression affecting alternative promoter usage and alternative splicing in Lewy body diseases.
    Original languageEnglish
    Pages (from-to)164-168
    JournalNeuroscience Letters
    Volume706
    DOIs
    Publication statusPublished - 27 Jul 2019

    Keywords

    • Dementia with Lewy bodies
    • Differential mRNA isoform expression
    • Lysosomal integral membrane protein type 2 gene – SCARB2
    • Parkinson's disease
    • Transcript variants
    • Transcription factor EB – TFEB

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