Martin A. Weber

Therapeutic safety implications of SARM1 active site inhibitors: subinhibitory concentrations cause neurodegeneration

Rebecca Leahey, Martin A. Weber, Chang Hoon Cho, Seong Kwon Hur et autres

SARM1, an octameric NADase, is a key regulator of axon degeneration and an emerging target in drug discovery to treat a range of neurodegenerative diseases. Recently, a structurally diverse series of adduct-forming, orthosteric SARM1 inhibitors have been discovered. Here, we show that …

Complement C3aR deletion does not attenuate neurodegeneration in a tauopathy model or alter acute inflammation-induced gene expression changes in the brain

Yuanyuan Wang, Shristi Pandey, Martin A. Weber, Man Kin Choy et autres

Abstract Aberrant activation of the classical complement pathway in the brain is implicated in contributing to synapse loss and neurodegeneration in various neurodegenerative conditions. Given that C3aR is a druggable target in the complement pathway, we evaluated the potential of C3aR KO …

Compound muscle action potential as an early functional in vivo measure of Sarm1 inhibition after sciatic nerve transection

Seong Kwon Hur, Rebecca Leahey, Mitchell Geringer, Chang Hoon Cho et autres

The NADase sterile alpha and TIR motif containing 1 (Sarm1) protein drives axon degeneration after injury. Loss or inhibition of Sarm1 structurally protects axons after sciatic nerve transection (SNT) in vivo but whether Sarm1 also drives functional loss after nerve injury is …

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Is online pathology education an effective and equitable approach for medical students?

Chaturaka Rodrigo, Simone L. Van Es, Karim Burkhardt, Stephanie Dowdell et autres

Introduction We assessed the performance of two cohorts of Australian medical students who were taught Pathology practical classes online or face-to-face, to see if online teaching creates an inequity in learning. Methods All medical students enrolled at the University of New South …

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Care Management für Menschen mit neuromuskulären Erkrankungen: Das Potential eines Beratungs- und Koordinationsdienstes

Veronika Waldboth, Christina Schuler, Georg Martin Stettner, Heidi Petry et autres

Neuromuskuläre Erkrankungen (NMD) können das Leben von betroffenen Kindern und Erwachsenen schwer beeinträchtigen. Die Behandlung ist oft komplex und involviert viele professionelle und informelle Dienste. Um diese Personengruppe bestmöglich zu unterstützen, wurde ein Tätigkeitsprofil für ein Care Management (CM) entwickelt. Mittels Mixed-Methods …

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Die Zufriedenheit von Menschen mit neuromuskulären Erkrankungen und ihren Angehörigen mit einem Beratungs- und Koordinationsdienst (Care Management): Eine Querschnittstudie

Veronika Waldboth, Iris Kramer, Christina Schuler, Martin A. Weber et autres

Die Versorgung von Menschen mit neuromuskulären Erkrankungen (NMD) ist komplex und erfordert einen koordinierten, interprofessionellen Ansatz. NMD Care Managerinnen können Betroffene und Angehörige durch Beratung und Koordination unterstützen und die interprofessionelle Zusammenarbeit im Behandlungsteam fördern. Ziel dieser Studie ist es die Zufriedenheit …

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Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer’s Disease and Multiple Sclerosis

Ainhoa Etxeberría, Yun‐An A. Shen, Stephen Vito, Sean M. Silverman et autres

Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's disease (AD) pathology and …

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A neuropathological perspective on fetal holocarboxylase synthetase deficiency

Kyra J. Lyell, Martin A. Weber, Antonia Shand, Rita Caldas et autres

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Polarized microtubule remodeling transforms the morphology of reactive microglia and drives cytokine release

Max Adrian, Martin A. Weber, Ming‐Chi Tsai, Caspar Glock et autres

Microglial reactivity is a pathological hallmark in many neurodegenerative diseases. During stimulation, microglia undergo complex morphological changes, including loss of their characteristic ramified morphology, which is routinely used to detect and quantify inflammation in the brain. However, the underlying molecular mechanisms and …

Comment on “Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice”

Yuanyuan Wang, Martin A. Weber, Oded Foreman, Helga Remy et autres

We highlight potential issues with a Western blot assay using mouse anti-caspase-1 antibody to detect cleaved caspase-1 p20 subunit in mouse brain tissue lysates.

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Uric Acid Deteriorates Load-Free Cell Shortening of Cultured Adult Rat Ventricular Cardiomyocytes via Stimulation of Arginine Turnover

Martin A. Weber, Rolf Schreckenberg, Klaus‐Dieter Schlüter

Hyperuricemia is a risk factor for heart disease. Cardiomyocytes produce uric acid via xanthine oxidase. The enzymatic reaction leads to oxidative stress in uric-acid-producing cells. However, extracellular uric acid is the largest scavenger of reactive oxygen species, specifically to nitrosative stress, which …

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NMDA receptor-dependent prostaglandin-endoperoxide synthase 2 induction in neurons promotes glial proliferation during brain development and injury

Jia Zhou, Yang Geng, Tonghui Su, Qiuyan Wang et autres

Astrocytes play critical roles in brain development and disease, but the mechanisms that regulate astrocyte proliferation are poorly understood. We report that astrocyte proliferation is bi-directionally regulated by neuronal activity via NMDA receptor (NMDAR) signaling in neurons. Prolonged treatment with an NMDAR …

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