{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:16:30Z","timestamp":1787163390196,"version":"build-2736575974"},"reference-count":39,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPD"],"published-print":{"date-parts":[[2021,10,12]]},"abstract":"<jats:p>Background: Gastrointestinal (GI) complications, that severely impact patient quality of life, are a common occurrence in patients with Parkinson\u2019s disease (PD). Damage to enteric neurons and the accumulation of alpha-synuclein in the enteric nervous system (ENS) are thought to contribute to this phenotype. Copper or iron chelators, that bind excess or labile metal ions, can prevent aggregation of alpha-synuclein in the brain and alleviate motor-symptoms in preclinical models of PD. Objective: We investigated the effect of ATH434 (formally PBT434), a small molecule, orally bioavailable, moderate-affinity iron chelator, on colonic propulsion and whole gut transit in A53T alpha-synuclein transgenic mice. Methods: Mice were fed ATH434 (30 mg\/kg\/day) for either 4 months (beginning at \u223c15 months of age), after the onset of slowed propulsion (\u201ctreatment group\u201d), or for 3 months (beginning at \u223c12 months of age), prior to slowed propulsion (\u201cprevention group\u201d). Results: ATH434, given after dysfunction was established, resulted in a reversal of slowed colonic propulsion and gut transit deficits in A53T mice to WT levels. In addition, ATH434 administered from 12 months prevented the slowed bead expulsion at 15 months but did not alter deficits in gut transit time when compared to vehicle-treated A53T mice. The proportion of neurons with nuclear Hu+ translocation, an indicator of neuronal stress in the ENS, was significantly greater in A53T than WT mice, and was reduced in both groups when ATH434 was administered. Conclusion: ATH434 can reverse some of the GI deficits and enteric neuropathy that occur in a mouse model of PD, and thus may have potential clinical benefit in alleviating the GI dysfunctions associated with PD.<\/jats:p>","DOI":"10.3233\/jpd-212731","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T13:05:54Z","timestamp":1628255154000},"page":"1821-1832","source":"Crossref","is-referenced-by-count":11,"title":["ATH434 Reverses Colorectal Dysfunction in the A53T Mouse Model of Parkinson\u2019s Disease"],"prefix":"10.1177","volume":"11","author":[{"given":"Shanti","family":"Diwakarla","sequence":"first","affiliation":[{"name":"Department of Medicine, Western Health, Melbourne University, Sunshine, VIC, Australia"},{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"McQuade","sequence":"additional","affiliation":[{"name":"Department of Medicine, Western Health, Melbourne University, Sunshine, VIC, Australia"},{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remy","family":"Constable","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Artaiz","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enie","family":"Lei","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Barnham","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"},{"name":"Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, VIC, Australia"},{"name":"Melbourne Dementia Research Centre, University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Adlard","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Cherny","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine R.","family":"Di Natale","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"},{"name":"Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-yi","family":"Chai","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria A.","family":"Lawson","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia"},{"name":"Department of Microbiology and Immunology and Peter Doherty Institute for Infection and Immunity, University of Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I.","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental 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