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Gastrointestinal tract cleavage of alpha-synuclein by asparaginyl endopeptidase leads to Parkinson's disease

8 months ago
Pathologic α-synuclein (α-syn) aggregates from the gastrointestinal (GI) tract may contribute to Parkinson's disease (PD). Xiang et al.¹ report in Neuron that enteric nervous system-specific expression of asparaginyl endopeptidase (AEP)-truncated α-syn and tau spreads to the brain, synergistically causing PD-related neurodegeneration and neurobehavioral deficits.
Longfei Li

Microbiota-derived lysophosphatidylcholine alleviates Alzheimer's disease pathology via suppressing ferroptosis

8 months ago
Alzheimer's disease (AD) is a pervasive neurodegenerative disorder, and new approaches for its prevention and therapy are critically needed. Here, we elucidate a gut-microbiome-brain axis that offers actionable perspectives for achieving this objective. Using the 5xFAD mouse model, we identify increased Clostridium abundance and decreased Bacteroides abundance as key features associated with β-amyloid (Aβ) burden. Treatment with Bacteroides ovatus, or its associated metabolite...
Xu Zha

SIRT6-dependent functional switch via K494 modifications of RE-1 silencing transcription factor

8 months ago
RE-1 silencing transcription factor (REST) is a key repressor of neural genes. REST is upregulated under stress signals, aging and neurodegenerative diseases, but although it is upregulated, its function is lost in Alzheimer's Disease. However, why it becomes inactive remains unclear. Here, we show that the NAD-dependent deacetylase SIRT6 regulates REST expression, location and activity. In the absence of SIRT6, REST is overexpressed but mislocalized, leading to a partial loss of its activity...
Adam Zaretsky