Broad proteomics analysis of seeding-induced aggregation of α-synuclein in M83 neurons reveals remodeling of proteostasis mechanisms that might contribute to Parkinson's disease pathogenesis.

Aggregation of misfolded α-synuclein (α-syn) is a key characteristic feature of Parkinson's disease (PD) and related synucleinopathies. The nature of these aggregates and their contribution to cellular dysfunction is still not clearly elucidated. We employed mass spectrometry-based total and phospho-proteomics to characterize the underlying molecular and biological changes due to α-syn aggregation using the M83 mouse primary neuronal model of PD.

Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.

Proximal spinal muscular atrophy (SMA) is a leading genetic cause for infant death in the world and results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of SMN protein and small molecules that can increase SMN expression are of considerable interest as potential therapeutics. Previous studies have shown that both 4-phenylbutyrate (4PBA) and trichostatin A (TSA) increase SMN expression in dermal fibroblasts derived from SMA patients.

Pharmacological mTOR-inhibition facilitates clearance of AD-related tau aggregates in the mouse brain.

In this study we aimed to reduce tau pathology, a hallmark of Alzheimer's Disease (AD), by activating mTOR-dependent autophagy in a transgenic mouse model of tauopathy by long-term dosing of animals with mTOR-inhibitors. Rapamycin treatment reduced the burden of hyperphosphorylated and aggregated pathological tau in the cerebral cortex only when applied to young mice, prior to the emergence of pathology. Conversely, PQR530 which exhibits better brain exposure and superior pharmacokinetic properties, reduced tau pathology even when the treatment started after the onset of pathology.

Preventing Childhood Adversity Through Economic Support and Social Norm Strategies.

Through the Essentials for Childhood program, the Centers for Disease Control and Prevention funds 7 state health departments (states) to address the urgent public health problem of adverse childhood experiences and child abuse and neglect, in particular. Through interviews and document reviews, the paper highlights the early implementation of 2 primary prevention strategies from the Centers for Disease Control and Prevention's child abuse and neglect technical package with the greatest potential for broad public health impact to prevent adverse childhood experiences-strengthening economic supports and changing social norms. States are focused on advancing family-friendly work policies such as paid family and medical leave, livable wage policies, flexible and consistent work schedules, as well as programs and policies that strengthen household financial security such as increasing access to Earned Income Tax Credit.

Supporting Local Health Departments to Lead Multisectoral Youth Violence Prevention Efforts.

This article examines organizational-level outcomes achieved during a technical assistance (TA) initiative designed to increase the capacity of local health departments (LHDs) to prevent youth violence (YV) via a multisectoral approach. This effort was designed to address the knowledge gap regarding how to provide effective TA to LHDs, specifically in YV. Twelve communities with high rates of YV were selected to participate using a multistage process.