Bruno A. Benitez

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...

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

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

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

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 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...

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 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.....

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 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...

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 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...

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 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...

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

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...

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....

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...

Lysosomal membrane homeostasis and its importance in physiology and disease www.nature.com/articles/s41...

Systematic analysis of cellular cross-talk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer’s disease An analysis of cell-cell communication in Alzheimer’s disease reveals insights into disease biology and potential therapeutic targets.

Systematic analysis of cellular cross-talk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer’s disease | Science Translational Medicine www.science.org/doi/10.1126/...

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...

Thanks to @erictopol.bsky.social for highlighting our study, led by Dr. @wrannlab.bsky.social , @mgbresearch.bsky.social & @harvardmed.bsky.social , with contributions from @tuckernr.bsky.social , @renhaol.bsky.social , & @kastanenka.bsky.social

Protective exercise responses in the dentate gyrus of Alzheimer’s disease mouse model revealed with single-nucleus RNA-sequencing - Nature Neuroscience 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...

Our latest collaboration on exercise & #Alzheimer's using #sn-RNA-Seq with Dr. Christiane Wrann @wrannlab.bsky.social @mgbresearch.bsky.social @harvardmed.bsky.social via @bidmcreseach.bsky.social @natneuro.nature.com www.nature.com/articles/s41...

JCI Insight - Stearoyl-CoA-Desaturase Inhibition normalizes brain lipid saturation, alpha-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice insight.jci.org/articles/vie...

TREM2 Activation by First-in-Class Direct Small Molecule Agonists: DEL Screening, Optimization, Biophysical Validation, and Functional Characterization https://www.biorxiv.org/content/10.1101/2025.05.22.655617v1

Excellent editorial by Dr. Saper on orexins in narcolepsy. @harvard-bidmc-pd.bsky.social @bidmcreseach.bsky.social @harvard.edu

Mechanism of Tau protein incorporation into exosomes via cooperative recognition of KFERQ-like motifs by LAMP2A and HSP70 Aggregates of the tau protein is a well-known hallmark of Alzheimer's disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau c…

Mechanism of Tau protein incorporation into exosomes via cooperative recognition of KFERQ-like motifs by LAMP2A and HSP70 www.sciencedirect.com/science/arti...

SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes Cellular senescence contributes to accelerated aging and the development of various neurodegeneration disorders including HIV-associated neurocognitive disorders. The development of HIV-associated neu...

SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes www.life-science-alliance.org/content/8/7/...

Rapid Response Bridge Funding Program In the face of recent abrupt shifts in federal funding for education research, including large-scale terminations of National Science Foundation (NSF) research grant awards, we have developed a rap...

I’m generally a cynic. Glass half empty kind of guy. But then I see something like this and think…there are good people out there. be positive and have hope. There is light in darkness. Early career scientists are being prioritized. Take a look! 🧪

www.spencer.org/grant_types/...

Cool stuff by the @malutansey.bsky.social lab

SLC7A11 is an unconventional H+ transporter in lysosomes SLC7A11 acts as an unconventional proton exporter in lysosomes regulating proteolytic degradation, ferroptotic cell death, and Parkinson’s disease pathology.

www.cell.com/cell/fulltex...

SMAD3 and PINK1 constitute a new positive feedback loop in regulation of mitophagy Mitophagy, selective degradation of dysfunctional mitochondria by the autophagy-lysosome pathway, is critical for maintaining cellular homeostasis. In recent years, significant progress has been ma...

SMAD3 and PINK1 constitute a new positive feedback loop in regulation of mitophagy www.tandfonline.com/doi/full/10....

Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson’s disease rupress.org/jcb/article/...

Characterization of Isolated Human Astrocytes from Aging Brain www.mdpi.com/1422-0067/26...

Lysosomal Dysfunction in Amyotrophic Lateral Sclerosis: A Familial Case Linked to the p.G376D TARDBP Mutation www.mdpi.com/1422-0067/26...

Sphingolipidoses: expanding the spectrum of α-synucleinopathies - Journal of Neural Transmission Although α-synuclein pathology is typically associated with Lewy body diseases and multiple systems atrophy, increasing evidence indicates that it also occurs in a group of lysosomal storage disorders...

Sphingolipidoses: expanding the spectrum of α-synucleinopathies link.springer.com/article/10.1...