P
Philip A. S. Lowden
Researcher at Birkbeck, University of London
Publications - 13
Citations - 1489
Philip A. S. Lowden is an academic researcher from Birkbeck, University of London. The author has contributed to research in topics: Polyketide & Huntington's disease. The author has an hindex of 12, co-authored 13 publications receiving 1430 citations. Previous affiliations of Philip A. S. Lowden include University of Exeter.
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Journal ArticleDOI
Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease
Emma Hockly,Victoria M. Richon,Benjamin Woodman,Donna L. Smith,Xianbo Zhou,E. Rosa,Kirupa Sathasivam,Shabnam Ghazi-Noori,Amarbirpal Mahal,Philip A. S. Lowden,Joan S. Steffan,J.L. Marsh,Leslie M. Thompson,Cathryn M. Lewis,Paul A. Marks,Gillian P. Bates +15 more
TL;DR: Preclinical trials with suberoylanilide hydroxamic acid (SAHA), a potent HDAC inhibitor, show that SAHA crosses the blood–brain barrier and increases histone acetylation in the brain, clearly validating the pursuit of this class of compounds as HD therapeutics.
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Minocycline and doxycycline are not beneficial in a model of Huntington's disease
Donna L. Smith,Benjamin Woodman,Amarbirpal Mahal,Kirupa Sathasivam,Shabnam Ghazi-Noori,Philip A. S. Lowden,Gillian P. Bates,Emma Hockly +7 more
TL;DR: It is shown that tetracyclines are potent inhibitors of huntingtin aggregation in a hippocampal slice culture model of HD at an effective concentration of 30μM, and cautioned that caution be exercised in proceeding into human clinical trials of minocycline.
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A brain-permeable small molecule reduces neuronal cholesterol by inhibiting activity of sirtuin 2 deacetylase.
David Taylor,Uma Balabadra,Zhongmin Xiang,Ben Woodman,Sarah Meade,Allison M. Amore,Michele M. Maxwell,Steven A. Reeves,Gillian P. Bates,Ruth Luthi-Carter,Philip A. S. Lowden,Aleksey G. Kazantsev +11 more
TL;DR: The identified SIRT2 inhibitor reduced cholesterol in cultured naïve neuronal cells and brain slices from wild-type mice and provides a clear opportunity for lead optimization and drug development, targeting metabolic dysfunctions in CNS disorders where abnormal cholesterol homeostasis is implicated.
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Evaluation of the benzothiazole aggregation inhibitors riluzole and PGL-135 as therapeutics for Huntington's disease
Emma Hockly,Jamie Tse,Amy L. Barker,Donna L. Moolman,Jean-Luc Beunard,Adrian Peter Revington,Kim Holt,Sunny Sunshine,Hilary Moffitt,Kirupa Sathasivam,Benjamin Woodman,Erich E. Wanker,Philip A. S. Lowden,Gillian P. Bates +13 more
TL;DR: To further explore the therapeutic potential of the benzothiazole aggregation inhibitors, PGL-135 and riluzole were assessed in hippocampal slice cultures derived from the R6/2 mouse, confirming their ability to inhibit aggregation with an EC50 of 40 microM in this system.
Journal ArticleDOI
New rapamycin derivatives by precursor-directed biosynthesis.
Philip A. S. Lowden,Philip A. S. Lowden,Günter A. Böhm,Su M. Metcalfe,James Staunton,Peter F. Leadlay +5 more
TL;DR: Results are described that promise to broaden the scope for biosynthetic engineering of new rapamycin and FK506/FK520 derivatives, and it is proposed that 4,5-dihydroxycyclohex-1-enecarboxylic acid is the most likely starter unit for the Rapamycin PKS.