Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents.

Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF and post-mortem brain of PD patients. Altered plasma and CSF PSAP levels correlate with PD-related motor impairments.

MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration.

The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPT mRNA internal ribosome entry site. MAPT encodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules.

Tau Isoform-Driven CBD Pathology Transmission in Oligodendrocytes in Humanized Tau Mice.

The aggregation of abnormally phosphorylated tau protein in neurons and glia is a neuropathological hallmark of several neurodegenerative disorders, collectively known as tauopathies. They are further subclassified based on the preferential pathological aggregation of three carboxyl-terminal repeat domains (3R) and/or 4R tau. Corticobasal degeneration (CBD) is a rare neurodegenerative disorder classified as a 4R tauopathy.

A GntR-Like Transcription Factor HypR Regulates Expression of Genes Associated With L-Hydroxyproline Utilization in A3(2).

Bacteria from the genus have been long exploited as the most prolific producers of antibiotics, other secondary metabolites and enzymes. They are important members of soil microbial communities that can adapt to changing conditions thank to the fine regulation of gene expression in response to environmental signals. A3(2) is a model organism for molecular studies with the most deeply recognized interactions within the complex metabolic and regulatory network.

α-synuclein-lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients.

The progressive accumulation, aggregation, and spread of α-synuclein (αSN) are common hallmarks of Parkinson's disease (PD) pathology. Moreover, numerous proteins interact with αSN species, influencing its toxicity in the brain. In the present study, we extended analyses of αSN-interacting proteins to cerebrospinal fluid (CSF).

Early synaptic dysfunction induced by α-synuclein in a rat model of Parkinson's disease.

Evidence suggests that synapses are affected first in Parkinson's disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats that overexpress human α-synuclein by local injection of viral-vectors in midbrain.