Jingyue Jia summarizes emerging insights into the global cellular responses to lysosomal damage, with particular emphasis on translational, metabolic, and transcriptional reprogramming, and highlights...

Levacetylleucine (Aqneursa™), an acetylated derivative and pro-drug of L-leucine, is the only FDA-approved monotherapy for Niemann–Pick disease type C (NPC). Its acetyl group enables transport via mon...

Ferroptosis is a unique form of programmed cell death that involves multiple organelles. Although traditionally viewed as a ‘degradation workshop’, accumulating evidence reveals that the lysosome serv...

This Review presents lysosomal dysfunction as a hallmark of ageing that drives age-related pathology, and highlights emerging therapeutic strategies that enhance lysosomal activity to promote healthy ...

Synaptic vesicle exocytosis and endocytosis are 2 fundamental processes that involve the coordinated and timely activity of many proteins and protein-lipid interactions. Alpha-synuclein (α-Syn) regulates several steps of these processes. Impaired exocytosis and endocytosis are important consequences …

Ferroptosis is a lipid peroxide-dependent form of cell death that occurs in degenerative conditions and may be leveraged for cancer therapy. Although …

Meng et al. show that deficiency of the lysosomal transmembrane protein TMEM106B contributes to Parkinson’s disease pathogenesis by accelerating α-synuclei

Human pancreatic cancer cells sense specific components of the ECM to fine-tune their autophagy flux levels, conferring the ability to coordinate proliferation, survival, and responsiveness to chemoth...

Improved technologies facilitate the detection of molecules linked to neurodegenerative brain changes at very low concentrations in the blood, complementing the clinical evaluation of suspected neurod...

Summary: Discoveries from the nematode C. elegans have provided insight into the many connections between immune responses and proteostasis, with examples of conservation across species.

Cells rely on regulated proteostasis mechanisms to keep their internal compartments functioning properly. When these mechanisms fail, damaged proteins accumulate, disrupting organelles, such as the n...

During starvation, TFEB activates SQSTM1-dependent autophagy to degrade ubiquitinated ribosomal components.

Lecanemab, a leading therapy for Alzheimer’s disease, induces an Fc-mediated transcriptional program in human microglia, linked to osteopontin and enhanced plaque phagocytosis, suggesting alternative ...

Neurons are highly polarised and compartmentalised cells with organelles that are specialised to support their spatial and functional demands. This includes lysosomes, which are single-membrane-bound ...

In the last two decades, many gene mutations have been identified that when homozygous, lead to childhood neurological disorders, but when heterozygou…

In the last two decades, many gene mutations have been identified that when homozygous, lead to childhood neurological disorders, but when heterozygous, result in adult-onset neurodegenerative disease. A shared feature linking these genes? They encode proteins residing in or impacting the function o …

Lysosomes are now known to play important roles in cell signaling and maintaining balance within cells. This Review explores how lysosomes interact with other cell parts and their role in diseases suc...

Abstract. Bi-allelic mutations in GBA1, a gene that encodes the lysosomal enzyme β-glucocerebrosidase (GCase), cause Gaucher disease (GD). Although GD carr

Primary tauopathies are a group of neurodegenerative diseases characterised by the aggregation of tau in the brain. In these diseases, little is known about the molecular mechanisms driving neurodege....

INTRODUCTION Alzheimer's disease (AD) shows clinical and molecular heterogeneity shaped by demographic and genetic factors. METHODS To resolve this heterogeneity, we performed a network-based prot...

Loss-of-function progranulin (GRN) mutations cause frontotemporal dementia. Most of these mutations cause haploinsufficiency of progranulin, a secreted pro-protein that has neurotrophic and anti-infl...

Most Alzheimer disease (AD) susceptibility genes have poorly understood roles in the central nervous system (CNS). To address this gap, we systematica…

Proteomics that elucidates PD mechanisms, provides reliable CSF and plasma biomarkers, and supports targeted therapies across the brain, cells, and overtime.

Lysosomes constitute the main degradative organelle of most eukaryotic cells and are capable of breaking down a wide spectrum of biomolecules, including proteins, lipids, glycans, and DNA/RNA. They p....

Autophagy is a highly conserved cellular pathway for the degradation and recycling of defective intracellular cargo and plays a vital role in the homeostasis of post-mitotic tissues, particularly t...

Lysosomes maintain cellular homeostasis by degrading proteins delivered via endocytosis and autophagy and recycling building blocks for organelle biogenesis. Lysosomal Storage Disorders (LSDs) compris...

Abstract. Amyloid precursor protein (APP), a type I transmembrane protein, is closely related to the pathogenesis of Alzheimer’s disease (AD). Amyloid beta

Abstract. EIPR1 (EARP-interacting protein 1, formerly known as TSSC1) is a WD40-domain protein that interacts with the EARP (endosome-associated recycling

Translational Psychiatry - LRRK2 deficiency mitigates amyloid β deposition-mediated pathology in a murine Alzheimer’s disease model by reprogramming microglia

Juvenile neuronal ceroid lipofuscinosis (JNCL) is an untreatable, fatal neurodegenerative lysosomal disease. Sleat and colleagues have shown that increased levels of tripeptidyl-peptide 1 attenuates d...

Objective Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for cleara.....

The amyloid precursor protein (APP) is cleaved by β- and γ-secretases, resulting in the generation of β-amyloid (Aβ). Aβ peptides accumulate in the brain of Alzheimer’s disease (AD), and the removal o...

Lysosomal damage impairs proteostasis and contributes to neurodegenerative diseases, yet cell-type-specific differences in lysosomal repair remain unclear. Using a neuron-astrocyte coculture system, w...

Lysosomes are essential for cell survival but are highly susceptible to diverse physical and pathological stressors. Thus, the ability to initiate an acute damage response and promote recovery after s...

Cryo-electron microscopy was used to study human mechanistic target of rapamycin complex 1 (mTORC1) activation on lysosomal membranes, showing progressive recruitment by RAG–Ragulator, RHEB and R...

Lysosomes degrade cellular components, and their membrane is an important signalling hub. Recent insights into the mechanisms that maintain lysosomal membrane homeostasis — including the interplay bet...

An analysis of cell-cell communication in Alzheimer’s disease reveals insights into disease biology and potential therapeutic targets.

Dissecting the adaptive exercise response of the neurogenic stem-cell niche in the dentate gyrus by single-nucleus RNA sequencing reveals the molecular mediators that underlie exercise’s protective ef...