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Bruno A. Benitez @benitezlab.bsky.social · 1d

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

Bruno A. Benitez @benitezlab.bsky.social · 2d

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

Bruno A. Benitez @benitezlab.bsky.social · 2d

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

Bruno A. Benitez @benitezlab.bsky.social · 2d

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

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Bruno A. Benitez @benitezlab.bsky.social · 2d

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

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Bruno A. Benitez @benitezlab.bsky.social · 2d

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

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Bruno A. Benitez @benitezlab.bsky.social · 10d

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

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Bruno A. Benitez @benitezlab.bsky.social · 21d

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

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Bruno A. Benitez @benitezlab.bsky.social · 21d

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

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Bruno A. Benitez @benitezlab.bsky.social · 21d

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

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Bruno A. Benitez @benitezlab.bsky.social · 21d

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

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Bruno A. Benitez @benitezlab.bsky.social · Aug 9

Microglia replacement halts the progression of microgliopathy in mice and humans | Science www.science.org/doi/full/10....

www.science.org

Bruno A. Benitez @benitezlab.bsky.social · Aug 5

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

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Bruno A. Benitez @benitezlab.bsky.social · Jul 30

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/...

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.

www.science.org

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Bruno A. Benitez @benitezlab.bsky.social · Jul 7

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...

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Bruno A. Benitez @benitezlab.bsky.social · Jun 12

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

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Bruno A. Benitez @benitezlab.bsky.social · Jun 12

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...

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...

www.nature.com

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Bruno A. Benitez @benitezlab.bsky.social · Jun 4

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...

JCI Insight - Stearoyl-CoA-Desaturase Inhibition normalizes brain lipid saturation, alpha-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice

insight.jci.org

Reposted by Bruno A. Benitez

bioRxiv Neuroscience @biorxiv-neursci.bsky.social · May 27

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

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Bruno A. Benitez @benitezlab.bsky.social · May 15

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

NEJM.org @nejm.org · May 14

In a new editorial, Clifford B. Saper, MD, PhD, describes the scientific foundations of a trial of an orexin agonist to treat narcolepsy. Read the full editorial: nej.md/4jUOItD

#MedSky #ScienceSky

Targeting Orexin Receptors to Treat Narcolepsy | NEJM

The author describes the scientific foundations of a trial of an orexin agonist to treat narcolepsy.

nej.md

Bruno A. Benitez @benitezlab.bsky.social · May 6

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

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…

www.sciencedirect.com

Bruno A. Benitez @benitezlab.bsky.social · May 6

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

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...

www.life-science-alliance.org

Reposted by Bruno A. Benitez

Dr Andrew Mahon @andyantarctica.bsky.social · May 3

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/...

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...

www.spencer.org

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Bruno A. Benitez @benitezlab.bsky.social · May 2

Cool stuff by the @malutansey.bsky.social lab

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Bruno A. Benitez @benitezlab.bsky.social · Apr 27

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

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