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GDNF Therapy : Can ...
GDNF Therapy : Can We Make It Work?
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- Björklund, Anders (författare)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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(creator_code:org_t)
- 2021
- 2021
- Engelska 4 s.
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 11:3, s. 1019-1022
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
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- In two recent postmortem studies, Jeffrey Kordower and colleagues report new findings that open up for an interesting discussion on the status of GDNF/NRTN signaling in patients with Parkinson's disease (PD), adding an interesting perspective on the, admittedly very limited, signs of restorative effects previously seen in GDNF/NRTN-treated patients. Their new findings show that the level of the GDNF signaling receptor Ret is overall reduced by about 65% relative to non-PD controls, and most severely, up to 80%, in nigral neurons containing α-synuclein inclusions, accompanied by impaired signaling downstream of the Ret receptor. Notably, however, the vast majority of the remaining nigral neurons retained a low level of Ret expression, and hence a threshold level of signaling. Further observations made in two patients who had received AAV-NRTN gene therapy 8-10 years earlier suggest the intriguing possibility that NRTN is able to restore Ret expression and upregulate its own signaling pathway. This "wind-up" mechanism, which is likely to depend on an interaction with dopaminergic transcription factor Nurr1, has therapeutic potential and should encourage renewed efforts to turn GDNF/NRTN therapy into success, once the recurring problem of under-dosing is resolved.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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