The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model
By Michelle onPublished: Tau neuronal aggregation is a driver of some neurodegenerative disorders. These toxic aggregates form when affected cells release aggregate seeds which are then internalized by unaffected cells. The authors show that a protein,Clusterin, delays Tau aggregation and suppresses seeding activity. View original preprint.
Longitudinal Analysis of Multiple Neurotransmitter Metabolites in Cerebrospinal Fluid in Early Parkinson’s Disease
By taliag onPublished: This study aimed to quantifiy multiple metabolites in CSF from PD versus healthy control subjects (HCs), including longitudinal analysis.
The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends
By Michelle onPublished: Irreversible toxic aggregates are a hallmark of neurodegenerative diseases, such as alpha-synuclein in PD. Using microfluidic diffusional sizing, the authors show that the molecular chaperone family Hsp70 (specifically Hsc70, DnaJB, and Apg2) can completely dissolve alpha-synuclein aggregation and revert it back to its monomeric state.
Quantitative proteomics reveals the selectivity of ubiquitin-binding autophagy receptors in the turnover of damaged lysosomes by lysophagy
By Michelle onPublished: The authors used proteomics to develop a quantitative snapshot of the proteins involved in lysophagy. Among the proteins identified, they found that TAX1BP1 and TBK1 are both required for lysophagy. View original preprint.
In situ architecture of neuronal α-Synuclein inclusions
By Michelle onPublished: Alpha-synuclein aggregation has been associated with Parkinson’s disease. Using cutting-edge imaging tools, the authors show neuronal alpha-synuclein inclusions within their native states. Further, they show that these aggregates are intermixed with cellular organelles and how aggregation spreads across the brain. View original preprint.
Seed Amplification Assay to Diagnose Early Parkinson’s and Predict Dopaminergic Deficit Progression
By taliag onPublished: This article uses an optimized high-throughput αS-SAA (based on a previously described α-Syn protein misfolding cyclic amplification (PMCA) assay)2, 5, 6 that detects αSyn aggregates in CSF, to evaluate 140 blinded samples from the Parkinson's Progression Markers Initiative (PPMI).
Vesicular dysfunction and pathways to neurodegeneration
By Michelle onIn this review, the pathways that have emerged as being critical for neuronal survival in the human brain is be discussed – illustrating the diversity of proteins and cellular events with three molecular case studies drawn from different neurological diseases.
A possible role for VPS13-family proteins in bulk lipid transfer, membrane expansion, and organelle biogenesis.
By Blythe Lloyd onReview: This review focuses on the structure and function of the VPS13 family of proteins and discusses the prevailing hypthoses in the field regarding its role in lipid transport.
From structure to ætiology: a new window on the biology of leucine-rich repeat kinase 2 and Parkinson’s disease
By Michelle onReview: This review summarizes LRRK2 structure both in a historical and current context, highlighting new insights into the structure of LRRK2 and complexes it forms.
Integrating protein networks and machine learning for disease stratification in the Hereditary Spastic Paraplegias
By Michelle onPublished: Hereditary Spastic Paraplegias are a group of neurodegenerative disorders with diverse clinical presentation and genetic variability. The authors used validated human data to create a protein-protein interaction map using causative genes to identify core proteins and processes. View original preprint.
Insights into VPS13 properties and function reveal a new mechanism of eukaryotic lipid transport
By Blythe Lloyd onReview: This review focuses on the disssecting the VPS13 family of proteins and their novel role in mediating lipid transfer between organelles.
Presynaptic autophagy is coupled to the synaptic vesicle cycle via ATG-9
By Blythe Lloyd onPublished: ATG9 is a core autophagy transmembrane protein present at nerve terminals. The authors found that ATG9 is a component of vesicles that undergo exo-endocytosis at synapses and that synaptojanin 1 mutations disrupt ATG9 activity at synapses. View original preprint.
VPS13D bridges the ER to mitochondria and peroxisomes via Miro
By Blythe Lloyd onPublished: VPS13C mutations are implicated in PD. The authors found that VPS13D, a closely related protein, can mediate a bridge between the peroxisome and different organelles (ER or mitochondria). Authors identified the specific ER and mitochondrial proteins facilitating this interaction resulting in dysregulation of lipid flux between them. View original preprint.
Dopamine transporter imaging predicts clinically‐defined α‐synucleinopathy in REM sleep behavior disorder
By taliag onPublished: This article describes the utility of using DAT SBR to identify individuals with iRBD with increased short-term risk of an aSN diagnosis.
Parkinson’s disease and cancer: a systematic re and meta-analysis of over 17 million participants
By Blythe Lloyd onPublished: The authors examined risk association between Parkinson’s disease and cancer using data from 63 publications, totaling in 17 million individuals. With the exception of melanoma, the authors found that the risk association of Parkinson’s disease and cancer was inversely related.
Structural basis for membrane recruitment of ATG16L1 by WIPI2 in autophagy
By taliag onPublished: Autophagy is a conserved mechanism for the sequestration and degradation of cytosolic cargo. ATG16L1 and WIPI2 are essential for autophagy initiation. The authors showed through structural determination how ATG16L1 and WIPI2 interact and compared the other WIPI proteins showing the variety of mechanisms of membrane recruitment by WIPI proteins. View original preprint.
It’s time to incorporate diversity into our basic science and disease models
By Blythe Lloyd onOp-Ed: This article discusses the need to incorporate diversity into basic science research and disease models.
Open science takes on Parkinson’s disease
By Blythe Lloyd onOp-Ed: This article explains the Aligning Science Across Parkinson's (ASAP) initiative's commitment to open science by taking a deep look into how the initiative contributes to the open science movement.
Coordinating a new approach to basic research into Parkinson’s disease
By Blythe Lloyd onOp-Ed: This article introduces the Aligning Science Across Parkinson's (ASAP) initiative by taking a deep dive into the planning of the initiative, scientific themes, objectives, and outlook.
Global ubiquitylation analysis of mitochondria in primary neurons identifies endogenous Parkin targets following activation of PINK1
By Blythe Lloyd onPublished: Loss-of-function mutations in Parkin cause disruption of mitophagy and are associated with PD. Yet, much of the biology surrounding Parkin function has taken place in artificial cell systems. The authors used human neurons to identify and validate 22 protein targets of Parkin, providing a functional Parkin landscape in neuronal cells.
