Glucocerebrosidase regulators SCARB2 and TFEB are up-regulated in Lewy body disease brain
Por:
Perez-Roca, L, Prada-Dacasa, P, Segu-Verges, C, Gamez-Valero, A, Serrano-Munoz, MA, Santos, C and Beyer, K
Publicada:
27 jul 2019
Ahead of Print:
19 may 2019
Categoría:
Neuroscience (miscellaneous)
Resumen:
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.
Filiaciones:
:
Hosp Univ, Dept Pathol, Barcelona, Spain
Hlth Sci Res Inst Germans Trias & Pujol, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Prada-Dacasa, P:
Univ Autonoma Barcelona, Barcelona, Spain
Segu-Verges, C:
Univ Autonoma Barcelona, Barcelona, Spain
Gamez-Valero, A:
Hosp Univ, Dept Pathol, Barcelona, Spain
Hlth Sci Res Inst Germans Trias & Pujol, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Serrano-Munoz, MA:
Hosp Univ, Dept Pathol, Barcelona, Spain
Hlth Sci Res Inst Germans Trias & Pujol, Barcelona, Spain
Santos, C:
Univ Autonoma Barcelona, Dept Biol Anim Biol Vegetal & Ecol, Unitat Antropol Biol, Barcelona, Spain
:
Hosp Univ, Dept Pathol, Barcelona, Spain
Hlth Sci Res Inst Germans Trias & Pujol, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
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