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Parkinson Disease: HELP
Articles by Todd P. Logan
Based on 3 articles published since 2010
(Why 3 articles?)

Between 2010 and 2020, Todd Logan wrote the following 3 articles about Parkinson Disease.
+ Citations + Abstracts
1 Article α-Synuclein promotes dilation of the exocytotic fusion pore. 2017

Logan, Todd / Bendor, Jacob / Toupin, Chantal / Thorn, Kurt / Edwards, Robert H. ·Departments of Neurology and Physiology, UCSF School of Medicine, University of California, San Francisco, San Francisco, California, USA. · Graduate Program in Biomedical Sciences, UCSF School of Medicine, University of California, San Francisco, San Francisco, California, USA. · Department of Biochemistry &Biophysics, UCSF School of Medicine, University of California, San Francisco, San Francisco, California, USA. ·Nat Neurosci · Pubmed #28288128.

ABSTRACT: The protein α-synuclein has a central role in the pathogenesis of Parkinson's disease. Like that of other proteins that accumulate in neurodegenerative disease, however, the function of α-synuclein remains unknown. Localization to the nerve terminal suggests a role in neurotransmitter release, and overexpression inhibits regulated exocytosis, but previous work has failed to identify a clear physiological defect in mice lacking all three synuclein isoforms. Using adrenal chromaffin cells and neurons, we now find that both overexpressed and endogenous synuclein accelerate the kinetics of individual exocytotic events, promoting cargo discharge and reducing pore closure ('kiss-and-run'). Thus, synuclein exerts dose-dependent effects on dilation of the exocytotic fusion pore. Remarkably, mutations that cause Parkinson's disease abrogate this property of α-synuclein without impairing its ability to inhibit exocytosis when overexpressed, indicating a selective defect in normal function.

2 Article The function of α-synuclein. 2013

Bendor, Jacob T / Logan, Todd P / Edwards, Robert H. ·Departments of Neurology and Physiology, Graduate Programs in Biomedical Sciences, Cell Biology and Neuroscience, UCSF School of Medicine, San Francisco, CA 94158-2517, USA. ·Neuron · Pubmed #24050397.

ABSTRACT: Human genetics has indicated a causal role for the protein α-synuclein in the pathogenesis of familial Parkinson's disease (PD), and the aggregation of synuclein in essentially all patients with PD suggests a central role for this protein in the sporadic disorder. Indeed, the accumulation of misfolded α-synuclein now defines multiple forms of neural degeneration. Like many of the proteins that accumulate in other neurodegenerative disorders, however, the normal function of synuclein remains poorly understood. In this article, we review the role of synuclein at the nerve terminal and in membrane remodeling. We also consider the prion-like propagation of misfolded synuclein as a mechanism for the spread of degeneration through the neuraxis.

3 Article Engineered disulfide bonds restore chaperone-like function of DJ-1 mutants linked to familial Parkinson's disease. 2010

Logan, Todd / Clark, Lindsay / Ray, Soumya S. ·Center for Neurologic Diseases, Brigham and Women's Hospital, Boston,Massachusetts 02115, USA. ·Biochemistry · Pubmed #20527929.

ABSTRACT: Loss-of-function mutations such as L166P, A104T, and M26I in the DJ-1 gene (PARK7) have been linked to autosomal-recessive early onset Parkinson's disease (PD). Cellular and structural studies of the familial mutants suggest that these mutations may destabilize the dimeric structure. To look for common dynamical signatures among the DJ-1 mutants, short MD simulations of up to 1000 ps were conducted to identify the weakest region of the protein (residues 38-70). In an attempt to stabilize the protein, we mutated residue Val 51 to cysteine (V51C) to make a symmetry-related disulfide bridge with the preexisting Cys 53 on the opposite subunit. We found that the introduction of this disulfide linkage stabilized the mutants A104T and M26I against thermal denaturation, improved their ability to scavenge reactive oxygen species (ROS), and restored a chaperone-like function of blocking alpha-synuclein aggregation. The L166P mutant was far too unstable to be rescued by introduction of the V51C mutation. The results presented here point to the possible development of pharmacological chaperones, which may eventually lead to PD therapeutics.