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Midnolin, a Genetic Risk Factor for Parkinson's Disease, Promotes Neurite Outgrowth Accompanied by Early Growth Response 1 Activation in PC12 Cells

5 months 3 weeks ago
Parkinson's disease (PD) is an age-related progressive neurodegenerative disease. Previously, we identified midnolin (MIDN) as a genetic risk factor for PD. Although MIDN copy number loss increases the risk of PD, the molecular function of MIDN remains unclear. To investigate the role of MIDN in PD, we established monoclonal Midn knockout (KO) PC12 cell models. Midn KO inhibited neurite outgrowth and neurofilament light chain (Nefl) gene expression. Although MIDN is mainly localized in the...
Ayano Chiba

Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer's disease

5 months 3 weeks ago
Alzheimer's disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed in human and animal studies. GABAergic interneurons (INs) within the hippocampus coordinate network activity, among which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide and calretinin play a crucial role. These cells provide primarily disinhibition to principal excitatory cells (PCs) in the hippocampal...
Felix Michaud

Cross-disorder and disease-specific pathways in dementia revealed by single-cell genomics

5 months 3 weeks ago
The development of successful therapeutics for dementias requires an understanding of their shared and distinct molecular features in the human brain. We performed single-nuclear RNA-seq and ATAC-seq in Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), analyzing 41 participants and ∼1 million cells (RNA + ATAC) from three brain regions varying in vulnerability and pathological burden. We identify 32 shared, disease-associated cell types and 14...
Jessica E Rexach

Phosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP

5 months 3 weeks ago
Microtubule-associated protein tau (MAPT/tau) accumulates in a family of neurodegenerative diseases, including Alzheimer's disease (AD). In disease, tau is aberrantly modified by post-translational modifications (PTMs), including hyper-phosphorylation. However, it is often unclear which of these PTMs contribute to tau's accumulation or what mechanisms might be involved. To explore these questions, we focus on a cleaved proteoform of tau (tauC3), which selectively accumulates in AD and was...
Cory M Nadel

Clearance and transport of amyloid beta by peripheral monocytes correlate with Alzheimer's disease progression

5 months 3 weeks ago
Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer's disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes...
Xin Huang