SNCA and TPPP transcripts increase in oligodendroglial cytoplasmic inclusions in multiple system atrophy

• DOI: 10.1016/j.nbd.2024.106551
• Publication Date: 2024-06-04T00:58:44Z
• Authors: Tomoya Kon; Shelley L. Forrest; Seojin Lee; Jun Li; Helen Chasiotis; Nasna Nassir; Mohammed J. Uddin; Anthony E. Lang; Gabor G. Kovacs
• Keywords: Cytoplasmic inclusion; Inclusion bodies

Multiple system atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-syn) in oligodendrocytes. The origin of α-syn accumulation GCIs unclear, particular whether abnormal aggregates result from the elevation endogenous expression MSA or ingested neuronal source. Tubulin polymerization promoting protein (TPPP) has been reported to play a crucial role developing GCI pathology. Here, total cell body, nucleus, and area density SNCA TPPP transcripts neurons oligodendrocytes with without various pathologies pontine base autopsy cases (n = 4) controls 2) were evaluated using RNAscope immunofluorescence. Single-nucleus RNA-sequencing data for was control frontal cortex 3). present nucleus cytoplasm both diseased, higher nuclear MSA. Area densities lower showing Indeed, unexpectedly found neurons, while anti-TPPP antibody failed detect immunoreactivity. revealed significant transcript predominantly oligodendrocytes, but also excitatory inhibitory neurons. This study addressed unclear accumulated GCIs, proposing that may supply templates misfolded α-syn. In addition, parallel behavior development highlights their potential synergistic contribution inclusion formation. conclusion, this advances our understanding pathogenesis, offers insights into dynamics formation, proposes regulating future molecular therapy