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.
Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain
By Michelle onPublished: Pathogenic mutations in LRRK2 are known to cause loss of primary cilia in neurons. The authors show that cilia loss is seen very early in mice harboring the most common LRRK2 mutation. Further, they show that this loss of cilia in astrocytes disrupted signaling pathways required for dopamine neuron maintenance. View original preprint.
Structural basis for the specificity of PPM1H phosphatase for Rab GTPases
By Michelle onPublished: LRRK2 acts by adding a phosphate group to enzymes known as Rab GTPases, which causes new biological events. The authors analyzed the structure of an enzyme, PPM1H, that counteracts LRRK2 by removing the phosphate group it adds to Rab GTPases. View original preprint.
High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease
By Blythe Lloyd onPublished: This article compared blinded cerebrospinal fluid (CSF) samples for a randomly selected subset of PPMI subjects (30 PD, 30 HC, and 20 SWEDD) and analyzed each in parallel using different αSyn-SAA protocols to understand the reproducability of aSyn-SAA as a diagnostic tool.
LRRK2 at Striatal Synapses: Cell-Type Specificity and Mechanistic Insights
By Blythe Lloyd onReview: This review focuses on pathogenic LRRK2 mutations and their effects on striatial neurons.