Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation
By savannah onPublished: Lipid transport at membrane contact sites is a critical biological process. The authors identify mitoguardin-2, a mitochondrial protein that functions as a lipid transporter at contact sites between the ER and/or lipid droplets. They show that mitoguardin-2 transfers glycerophospholipids between membranes in vitro.
Endoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration
By quincy.tichenor onReview: Several mutations of genes that encode proteins localized at the endoplasmic reticulum membrane contact sites result in familial neurodegenerative diseases. Here, the authors provide an overview of such diseases, with a specific focus on proteins that directly or indirectly impact lipid transport.
Neuronal hyperactivity–induced oxidant stress promotes in vivo α-synuclein brain spreading
By quincy.tichenor onPublished: This study investigated the relationship between neuronal activity and interneuronal transfer of α-synuclein, a Parkinson-associated protein, and elucidated mechanisms underlying this relationship.
Genetic variations in GBA1 and LRRK2 genes: Biochemical and clinical consequences in Parkinson disease
By quincy.tichenor onReview: This review compares GBA1 and LRRK2-associated PD, and highlights possible genotype-phenotype associations for GBA1 and LRRK2 separately, based on biochemical consequences of single variants.
Mechanisms controlling selective elimination of damaged lysosomes
By quincy.tichenor onReview: This review discusses the current state of our understanding of mechanisms used to mark and eliminate damaged lysosomes, and discuss the complexities of galectin function and ubiquitin-chain linkage types. Authors also discuss the limitations of available data and challenges with the goal of understanding the mechanistic basis of key steps in lysophagic flux.
P5B-ATPases in the mammalian polyamine transport system and their role in disease
By quincy.tichenor onReview: This review brings together the current knowledge of the cellular function of the mammalian polyamine transport system, focusing on the role of P5B-ATPases ATP13A2-5.
Multi-ancestry genome-wide meta-analysis in Parkinson’s disease
By quincy.tichenor onPublished: The authors performed the first large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases, and 2,458,063 controls, including individuals of European, East Asian, Latin American, and African ancestry. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations. View original preprint.
Membrane remodeling properties of the Parkinson’s disease protein LRRK2
By quincy.tichenor onPreprint: The authors examine how purified LRRK2 directly binds acidic lipid bilayers in a cell-free system and can deform them into narrow tubules in a guanylnucleotide-dependent but ATP-independent way.
Cellular senescence: a key therapeutic target in aging and diseases
By quincy.tichenor onReview: This review discusses the role of SnCs in aging and age-related diseases, strategies to target SnCs, approaches to discover and develop senotherapeutics, and preclinical and clinical advances of senolytics.
Disruption of lysosomal proteolysis in astrocytes facilitates midbrain proteostasis failure in an early-onset PD model
By quincy.tichenor onPublished: Accumulation of advanced glycation end products (AGEs) on biopolymers accompany cellular aging and drives poorly understood disease processes. Here, authors studied how AGEs contribute to development of early on-set Parkinson’s disease (PD) caused by loss-of-function of DJ1, a protein deglycase. View original preprint.
A Markov random field model-based approach for differentially expressed gene detection from single-cell RNA-seq data
By Blythe Lloyd onThe MARBLES, a Markov Random Field model-based approach for differentially expressed gene detection from scRNA-seq data can capture cell-type relationships and account for sample variation by modeling cell-type-specific pseudobulk data. The authors used simulation results to compare this approach to existing methods from two scRNA-seq datasets.
Mechanisms underlying ubiquitin-driven selective mitochondrial and bacterial autophagy
By Blythe Lloyd onReview: The authors review recent efforts to understand the biochemical mechanisms and principles by which cargo are marked with ubiquitin and how ubiquitin-binding cargo receptors use conserved structural modules to recruit the autophagosome initiation machinery, with a particular focus on mitochondria and intracellular bacteria as cargo.
GBA Variants and Parkinson Disease: Mechanisms and Treatments
By Blythe Lloyd onReview: The GBA gene encodes for the lysosomal enzyme glucocerebrosidase (GCase). Around 5–15% of PD patients have mutations in the GBA gene. This review discusses the pathways associated with GBA-PD and highlights potential treatments which may act to target GCase and prevent neurodegeneration.
Lyso-IP: Uncovering Pathogenic Mechanisms of Lysosomal Dysfunction
By Blythe Lloyd onReview: The development of the Lyso-IP approach and similar methods now allow for lysosomal purification within ten minutes. This review discusses the impact of this new methodology in uncovering the role of lysosomes in neurodegenerative conditions.
Similarities and differences between nigral and enteric dopaminergic neurons unravel distinctive involvement in Parkinson’s disease
By Blythe Lloyd onReview: In this comparative review, authors compare the Dopamine neurons in the enteric nervous system, substantia nigra pars compacta, and ventral tegemental area, to assess whether, independent of their location or function, it is sufficient for neurons to be dopaminergic to be selectively vulnerable during the progression of PD.
Black and African American Connections to Parkinson’s Disease Study: Addressing Missing Diversity in Parkinson’s Disease Genetics
By Blythe Lloyd onOp-Ed: This article discusses the GP2 Black and African American Connections to Parkinson's Disease (BLAAC PD) study.
The chaperone Clusterin in neurodegeneration−friend or foe?
By Blythe Lloyd onReview: The authors review the diverse functions of Clusterin in the pathogenesis of neurodegenerative diseases, focusing on evidence that Clusterin may act either as a suppressor or enhancer of pathology.
Neuropathological Features of Gaucher Disease and Gaucher Disease with Parkinsonism
By Blythe Lloyd onReview: To better understand the disease pathogenesis of Gaucher Disease, the authors reviewed the neuropathological features associated with glucocerebrosidase deficiency, examining autopsy studies of rare patients with GD.
Immune senescence, immunosenescence, and aging
By Blythe Lloyd onReview: This review focuses on age-related immune dysfunction, cellular senescence and the impaired immune response to pathogens.
A unifying model for the role of the ATG8 system in autophagy
By Blythe Lloyd onReview: The core ATG8 system is one of the most-studied autophagy components. Here, authors reconcile prior observations of the core ATG8 system into a unifying model. Bypass pathways of autophagy that function independently of the core ATG8 system are also discussed.
