Bruno A. Benitez
@benitezlab.bsky.social
Benitez Lab at BIDMC-HMS; Alzheimer's, Parkinson's, Omics, Genetics, Autophagy-Lysosomal pathway
Pinned
Our latest review on the role of CSPα/DNAJC5 in neurodegenerative dementia #ANCL #Alzheimer #Parkinson #ALS #Huntington by a postdoc in the lab: Dr. Matthew Rosene @bidmcreseach.bsky.social @harvardmed.bsky.social via npj dementia www.nature.com/articles/s44...
The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases www.sciencedirect.com/science/arti...
The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases
In the last two decades, many gene mutations have been identified that when homozygous, lead to childhood neurological disorders, but when heterozygou…
www.sciencedirect.com
November 19, 2025 at 4:16 PM
The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases www.sciencedirect.com/science/arti...
The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases pubmed.ncbi.nlm.nih.gov/41253210/
The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases - PubMed
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 …
pubmed.ncbi.nlm.nih.gov
November 19, 2025 at 2:07 PM
The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases pubmed.ncbi.nlm.nih.gov/41253210/
Failure of lysosomal acidification and endomembrane network in neurodegeneration www.nature.com/articles/s12...
Failure of lysosomal acidification and endomembrane network in neurodegeneration - Experimental & Molecular Medicine
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...
www.nature.com
November 19, 2025 at 2:06 PM
Failure of lysosomal acidification and endomembrane network in neurodegeneration www.nature.com/articles/s12...
Inhibition or genetic reduction of ASAH1/acid ceramidase restore α-synuclein clearance in mutant GBA1 dopamine neurons from #Parkinson’s patients academic.oup.com/hmg/advance-...
Inhibition or genetic reduction of ASAH1/acid ceramidase restore α-synuclein clearance in mutant GBA1 dopamine neurons from Parkinson’s patients
Abstract. Bi-allelic mutations in GBA1, a gene that encodes the lysosomal enzyme β-glucocerebrosidase (GCase), cause Gaucher disease (GD). Although GD carr
academic.oup.com
November 13, 2025 at 4:42 PM
Inhibition or genetic reduction of ASAH1/acid ceramidase restore α-synuclein clearance in mutant GBA1 dopamine neurons from #Parkinson’s patients academic.oup.com/hmg/advance-...
Highly recommended review. "recent convergence of large-scale biobanks, #multi-omics data and computational methods, including machine learning, has led to advances in #genetics-driven drug discovery, offering new opportunities to refine target selection and reduce late-stage risk"
New online! Genomics of drug target prioritization for complex diseases
Genomics of drug target prioritization for complex diseases
Nature Reviews Genetics, Published online: 06 November 2025; doi:10.1038/s41576-025-00904-4In this Review, Chen et al. discuss how the advancement and integration of large-scale genetic resources, multi-omics data and sophisticated computational tools are improving drug development pipelines.
www.nature.com
November 6, 2025 at 3:45 PM
Highly recommended review. "recent convergence of large-scale biobanks, #multi-omics data and computational methods, including machine learning, has led to advances in #genetics-driven drug discovery, offering new opportunities to refine target selection and reduce late-stage risk"
Leveraging #Proteomics to Explore the Molecular Mechanisms of Primary Tauopathies - Nementzik - 2025 - Journal of Neurochemistry - Wiley Online Library onlinelibrary.wiley.com/doi/10.1111/...
Leveraging Proteomics to Explore the Molecular Mechanisms of Primary Tauopathies
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....
onlinelibrary.wiley.com
November 3, 2025 at 1:26 PM
Leveraging #Proteomics to Explore the Molecular Mechanisms of Primary Tauopathies - Nementzik - 2025 - Journal of Neurochemistry - Wiley Online Library onlinelibrary.wiley.com/doi/10.1111/...
Proteomic subtyping of #Alzheimer's disease CSF links blood–brain barrier dysfunction to reduced levels of tau and #synaptic biomarkers - Bangs - 2025 - Alzheimer's & Dementia - Wiley Online Library alz-journals.onlinelibrary.wiley.com/doi/10.1002/...
Proteomic subtyping of Alzheimer's disease CSF links blood–brain barrier dysfunction to reduced levels of tau and synaptic biomarkers
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...
alz-journals.onlinelibrary.wiley.com
November 3, 2025 at 1:25 PM
Proteomic subtyping of #Alzheimer's disease CSF links blood–brain barrier dysfunction to reduced levels of tau and #synaptic biomarkers - Bangs - 2025 - Alzheimer's & Dementia - Wiley Online Library alz-journals.onlinelibrary.wiley.com/doi/10.1002/...
Delivering Progranulin to Astrocytic #Lysosomes Promotes Growth of Co‐Cultured Neurons - Kaplelach - 2025 - Journal of Neurochemistry - Wiley Online Library onlinelibrary.wiley.com/doi/10.1111/...
Delivering Progranulin to Astrocytic Lysosomes Promotes Growth of Co‐Cultured Neurons
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...
onlinelibrary.wiley.com
November 3, 2025 at 1:23 PM
Delivering Progranulin to Astrocytic #Lysosomes Promotes Growth of Co‐Cultured Neurons - Kaplelach - 2025 - Journal of Neurochemistry - Wiley Online Library onlinelibrary.wiley.com/doi/10.1111/...
Revealing the nervous system requirements of #Alzheimer disease risk genes in Drosophila www.sciencedirect.com/science/arti...
Revealing the nervous system requirements of Alzheimer disease risk genes in Drosophila
Most Alzheimer disease (AD) susceptibility genes have poorly understood roles in the central nervous system (CNS). To address this gap, we systematica…
www.sciencedirect.com
October 31, 2025 at 3:34 PM
Revealing the nervous system requirements of #Alzheimer disease risk genes in Drosophila www.sciencedirect.com/science/arti...
Proud to guest edit an npj Parkinson’s Disease Collection: “Proteomics to Transform Parkinson’s Disease.” Submissions open through 27 Jul 2026. Details & submit: www.nature.com/collections/...
#Parkinsons #Proteomics #PDResearch
#Parkinsons #Proteomics #PDResearch
Proteomics to Transform Parkinson’s Disease: Mechanisms, Biomarkers, and Therapeutic Targets
Proteomics that elucidates PD mechanisms, provides reliable CSF and plasma biomarkers, and supports targeted therapies across the brain, cells, and overtime.
www.nature.com
October 28, 2025 at 1:54 PM
Proud to guest edit an npj Parkinson’s Disease Collection: “Proteomics to Transform Parkinson’s Disease.” Submissions open through 27 Jul 2026. Details & submit: www.nature.com/collections/...
#Parkinsons #Proteomics #PDResearch
#Parkinsons #Proteomics #PDResearch
Proteomics Insights Into #Lysosome Biogenesis and Maturation analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...
Proteomics Insights Into Lysosome Biogenesis and Maturation
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....
analyticalsciencejournals.onlinelibrary.wiley.com
October 16, 2025 at 2:47 PM
Proteomics Insights Into #Lysosome Biogenesis and Maturation analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...
The space-time continuum in neurological disorders of the #autophagosome-#lysosome fusion machinery www.tandfonline.com/doi/full/10....
The space-time continuum in neurological disorders of the autophagosome-lysosome fusion machinery
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...
www.tandfonline.com
October 16, 2025 at 2:46 PM
The space-time continuum in neurological disorders of the #autophagosome-#lysosome fusion machinery www.tandfonline.com/doi/full/10....
Proteome Landscapes Decode Organelle Vulnerabilities in cortical and dopaminergic-like induced neurons across #Lysosomal Storage Disorders by the Harper Lab at @harvardcellbio.bsky.social www.biorxiv.org/content/10.1...
Proteome Landscapes Decode Organelle Vulnerabilities in cortical and dopaminergic-like induced neurons Across Lysosomal Storage Disorders
Lysosomes maintain cellular homeostasis by degrading proteins delivered via endocytosis and autophagy and recycling building blocks for organelle biogenesis. Lysosomal Storage Disorders (LSDs) compris...
www.biorxiv.org
October 8, 2025 at 3:20 PM
Proteome Landscapes Decode Organelle Vulnerabilities in cortical and dopaminergic-like induced neurons across #Lysosomal Storage Disorders by the Harper Lab at @harvardcellbio.bsky.social www.biorxiv.org/content/10.1...
APP ubiquitination by VHL protein is essential for MVB sorting and #lysosomal degradation academic.oup.com/jmcb/advance...
APP ubiquitination by VHL protein is essential for MVB sorting and lysosomal degradation
Abstract. Amyloid precursor protein (APP), a type I transmembrane protein, is closely related to the pathogenesis of Alzheimer’s disease (AD). Amyloid beta
academic.oup.com
October 8, 2025 at 12:39 PM
APP ubiquitination by VHL protein is essential for MVB sorting and #lysosomal degradation academic.oup.com/jmcb/advance...
EIPR1 variants cause a neurodevelopmental disorder with endolysosomal and dense core vesicle defects by Dr. Bonifacino lab at NIH academic.oup.com/brain/advanc...
EIPR1 variants cause a neurodevelopmental disorder with endolysosomal and dense core vesicle defects
Abstract. EIPR1 (EARP-interacting protein 1, formerly known as TSSC1) is a WD40-domain protein that interacts with the EARP (endosome-associated recycling
academic.oup.com
October 8, 2025 at 12:35 PM
EIPR1 variants cause a neurodevelopmental disorder with endolysosomal and dense core vesicle defects by Dr. Bonifacino lab at NIH academic.oup.com/brain/advanc...
LRRK2 deficiency mitigates amyloid β deposition-mediated pathology in a murine Alzheimer’s disease model by reprogramming microglia ... 🤔 rdcu.be/eJRBe
LRRK2 deficiency mitigates amyloid β deposition-mediated pathology in a murine Alzheimer’s disease model by reprogramming microglia
Translational Psychiatry - LRRK2 deficiency mitigates amyloid β deposition-mediated pathology in a murine Alzheimer’s disease model by reprogramming microglia
rdcu.be
October 7, 2025 at 1:25 PM
LRRK2 deficiency mitigates amyloid β deposition-mediated pathology in a murine Alzheimer’s disease model by reprogramming microglia ... 🤔 rdcu.be/eJRBe
Elevated tripeptidyl-peptidase 1 corrects multiple disease phenotypes in a mouse model of juvenile neuronal ceroid lipofuscinosis: Molecular Therapy Methods & Clinical Development www.cell.com/molecular-th...
Elevated tripeptidyl-peptidase 1 corrects multiple disease phenotypes in a mouse model of juvenile neuronal ceroid lipofuscinosis
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...
www.cell.com
October 7, 2025 at 1:18 PM
Elevated tripeptidyl-peptidase 1 corrects multiple disease phenotypes in a mouse model of juvenile neuronal ceroid lipofuscinosis: Molecular Therapy Methods & Clinical Development www.cell.com/molecular-th...
Mutations in the Key Autophagy Tethering Factor EPG5 Link Neurodevelopmental and Neurodegenerative Disorders Including Early‐Onset Parkinsonism - Dafsari - Annals of Neurology - Wiley Online Library onlinelibrary.wiley.com/doi/10.1002/...
Mutations in the Key Autophagy Tethering Factor EPG5 Link Neurodevelopmental and Neurodegenerative Disorders Including Early‐Onset Parkinsonism
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.....
onlinelibrary.wiley.com
October 7, 2025 at 1:16 PM
Mutations in the Key Autophagy Tethering Factor EPG5 Link Neurodevelopmental and Neurodegenerative Disorders Including Early‐Onset Parkinsonism - Dafsari - Annals of Neurology - Wiley Online Library onlinelibrary.wiley.com/doi/10.1002/...
APP family is a regulator of endo-lysosomal membrane vulnerability www.jbc.org/article/S002...
APP family is a regulator of endo-lysosomal membrane vulnerability
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...
www.jbc.org
September 30, 2025 at 11:33 AM
APP family is a regulator of endo-lysosomal membrane vulnerability www.jbc.org/article/S002...
Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons www.biorxiv.org/content/10.1...
Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons
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...
www.biorxiv.org
September 18, 2025 at 1:15 PM
Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons www.biorxiv.org/content/10.1...
Processing bodies promote lysosomal quality control and cell survival during recovery from lysosomal damage pubmed.ncbi.nlm.nih.gov/40964023/
Processing bodies promote lysosomal quality control and cell survival during recovery from lysosomal damage - PubMed
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...
pubmed.ncbi.nlm.nih.gov
September 18, 2025 at 1:14 PM
Processing bodies promote lysosomal quality control and cell survival during recovery from lysosomal damage pubmed.ncbi.nlm.nih.gov/40964023/
Targeted autophagic clearance of Tau protects against Alzheimer's disease through amelioration of Tau-mediated lysosomal stress www.thno.org/v15p9240.htm
Targeted autophagic clearance of Tau protects against Alzheimer's disease through amelioration of Tau-mediated lysosomal stress
www.thno.org
September 18, 2025 at 1:13 PM
Targeted autophagic clearance of Tau protects against Alzheimer's disease through amelioration of Tau-mediated lysosomal stress www.thno.org/v15p9240.htm
Structural basis for mTORC1 activation on the lysosomal membrane www.nature.com/articles/s41...
Structural basis for mTORC1 activation on the lysosomal membrane - Nature
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...
www.nature.com
September 18, 2025 at 1:12 PM
Structural basis for mTORC1 activation on the lysosomal membrane www.nature.com/articles/s41...
Microglia replacement halts the progression of microgliopathy in mice and humans | Science www.science.org/doi/full/10....
www.science.org
August 9, 2025 at 12:03 PM
Microglia replacement halts the progression of microgliopathy in mice and humans | Science www.science.org/doi/full/10....
Lysosomal membrane homeostasis and its importance in physiology and disease www.nature.com/articles/s41...
Lysosomal membrane homeostasis and its importance in physiology and disease - Nature Reviews Molecular Cell Biology
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...
www.nature.com
August 5, 2025 at 1:10 PM
Lysosomal membrane homeostasis and its importance in physiology and disease www.nature.com/articles/s41...