Alexander J. Whitworth

Cross-platform multi-laboratory screening identifies HUWE1, USP33 and USP20 as negative-regulators of autophagy or mitophagy with relevance to neurodegeneration

The paper identifies HUWE1, USP33, and USP20 as negative regulators of autophagy/mitophagy through cross-platform screening and validates their roles in neurodegeneration using multiple models.

Essential conserved neuronal motors kinesin-1 and kinesin-3 regulate Abeta42 toxicity in vivo

This study shows that kinesin-1 and kinesin-3 mitigate Aβ42Arc toxicity in Drosophila neurons and rescue behavioral defects.

Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions

This study shows that Clu/Clu1 proteins form mitochondrial-associated granules and regulate mitochondrial protein translation by interacting with ribosomes and mRNAs during metabolic transitions.

Activation of the Keap1/Nrf2 pathway suppresses mitochondrial dysfunction in C9orf72 ALS/FTD in vivo models and patient iNeurons

This study shows that activating the Keap1/Nrf2 pathway reduces mitochondrial dysfunction and motor deficits in C9orf72 ALS/FTD models and patient-derived neurons.

N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity

The paper shows that N-terminal acetylation by NatC protects proteins from degradation, enhancing longevity and motility, and that UBR4-KCMF1 targets unacetylated N-terminal Met followed by hydrophobic residues.

FBXO7/ntc and USP30 antagonistically set the ubiquitination threshold for basal mitophagy and provides a target for Pink1 phosphorylation in vivo

The paper shows FBXO7/ntc and USP30 regulate basal mitophagy through opposing ubiquitination and deubiquitination mechanisms, with implications for Parkinson's disease therapy.

Mitochondrial CISD1/Cisd accumulation blocks mitophagy and genetic or pharmacological inhibition rescues neurodegenerative phenotypes in Pink1/parkin models

A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export suppresses neurodegeneration

This paper develops a cell-penetrant peptide that blocks C9ORF72-repeat RNA nuclear export, reducing neurodegeneration in preclinical models of ALS and FTD.

Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson's disease at Chr16q11.2 and on the MAPT H1 allele

The paper identifies KAT8 and KANSL1 as regulators of PINK1-mitophagy linked to Parkinson's disease risk, suggesting a novel pathway for therapeutic targeting.

A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit

This study identifies a late-stage quality control step in human mitochondrial ribosome large subunit assembly, showing that MRM2 ablation impairs oxidative phosphorylation through defective translation and accumulation of assembly intermediates.

Safety and efficacy of C9ORF72-repeat RNA nuclear export inhibition in amyotrophic lateral sclerosis

This study shows that inhibiting SRSF1-dependent nuclear export of C9ORF72-repeat transcripts in ALS models protects neurons and identifies key RNA changes involved in disease.

Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration

This study shows mitochondrial impairment triggers Wallerian-like axon degeneration by depleting NMNAT2, activating SARM1, and replicating key steps of the Wallerian pathway in mice and flies.

The STING pathway does not contribute to Pink1/parkin phenotypes in Drosophila

This study shows that the STING pathway does not contribute to Pink1/parkin phenotypes in Drosophila, contrasting findings in mice.