A sensitive period for the development of episodic-like memory in mice.

Episodic-like memory is a later-developing cognitive function supported by the hippocampus. In mice, the formation of extracellular perineuronal nets in subfield CA1 of the dorsal hippocampus controls the emergence of episodic-like memory during the fourth postnatal week (Ramsaran et al., 2023).

Disrupting the α-synuclein-ESCRT interaction with a peptide inhibitor mitigates neurodegeneration in preclinical models of Parkinson's disease.

Accumulation of α-synuclein into toxic oligomers or fibrils is implicated in dopaminergic neurodegeneration in Parkinson's disease. Here we performed a high-throughput, proteome-wide peptide screen to identify protein-protein interaction inhibitors that reduce α-synuclein oligomer levels and their associated cytotoxicity. We find that the most potent peptide inhibitor disrupts the direct interaction between the C-terminal region of α-synuclein and CHarged Multivesicular body Protein 2B (CHMP2B), a component of the Endosomal Sorting Complex Required for Transport-III (ESCRT-III).

Hazardous alcohol use and alcohol-related harm in rural and remote communities: a scoping review.

Alcohol use is a major risk factor for death and disease worldwide and alcohol-related harms appear to be more prevalent in rural and remote, relative to urban, communities. This Review synthesised international research on rural-urban disparities in hazardous and harmful alcohol use and risk factors for these outcomes within rural and remote communities. 280 studies from 49 countries were included in the Scoping Review.

Deep Brain Stimulation of the Medial Septal Nucleus Induces Expression of a Virally Delivered Reporter Gene in Dentate Gyrus.

Background: Mechanisms of deep brain stimulation (DBS) remain controversial, and spatiotemporal control of brain-wide circuits remains elusive. Adeno-associated viral (AAV) vectors have emerged as vehicles for spatiotemporal expression of exogenous transgenes in several tissues, including specific nuclei in the brain. Coupling DBS with viral vectors to modulate exogenous transgene expression remains unexplored.

Early-onset impairment of the ubiquitin-proteasome system in dopaminergic neurons caused by α-synuclein.

Parkinson's disease is a progressive neurodegenerative disorder characterised by the accumulation of misfolded α-synuclein in selected brain regions, including the substantia nigra pars compacta (SNpc), where marked loss of dopaminergic neurons is also observed. Yet, the relationship between misfolded α-synuclein and neurotoxicity currently remains unclear. As the principal route for degradation of misfolded proteins in mammalian cells, the ubiquitin-proteasome system (UPS) is critical for maintenance of cellular proteostasis.

Bcl-2-associated athanogene 5 (BAG5) regulates Parkin-dependent mitophagy and cell death.

As pathogenic Parkin mutations result in the defective clearance of damaged mitochondria, Parkin-dependent mitophagy is thought to be protective against the dopaminergic neurodegeneration observed in Parkinson's disease. Recent studies, however, have demonstrated that Parkin can promote cell death in the context of severe mitochondrial damage by degrading the pro-survival Bcl-2 family member, Mcl-1. Therefore, Parkin may act as a 'switch' that can shift the balance between protective or pro-death pathways depending on the degree of mitochondrial damage.