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Galectin-3 shapes t...
Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease
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- García-Revilla, Juan (författare)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups,University Hospital Virgen del Rocío,University of Seville
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- Boza-Serrano, Antonio (författare)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups,University Hospital Virgen del Rocío,University of Seville
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- Jin, Yiyun (författare)
- Imperial College London
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- Vadukul, Devkee M. (författare)
- Imperial College London
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- Soldán-Hidalgo, Jesús (författare)
- University Hospital Virgen del Rocío,University of Seville
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- Camprubí-Ferrer, Lluís (författare)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- García-Cruzado, Marta (författare)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Martinsson, Isak (författare)
- Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups
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- Klementieva, Oxana (författare)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Medicinsk mikrospektroskopi,Forskargrupper vid Lunds universitet,LINXS - Institute of advanced Neutron and X-ray Science,Kemiska institutionen,Institutioner vid LTH,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Medical Microspectroscopy,Lund University Research Groups,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas
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- Ruiz, Rocío (författare)
- University Hospital Virgen del Rocío,University of Seville
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- Aprile, Francesco A. (författare)
- Imperial College London
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- Deierborg, Tomas (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Neuroinflammation,Forskargrupper vid Lunds universitet,Department of Experimental Medical Science,Faculty of Medicine,Lund University Research Groups
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- Venero, José Luis (författare)
- University Hospital Virgen del Rocío,University of Seville
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(creator_code:org_t)
- 2023
- 2023
- Engelska 25 s.
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Ingår i: Acta Neuropathologica. - 0001-6322. ; 146:1, s. 51-75
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Parkinson’s Disease (PD) is a neurodegenerative and progressive disorder characterised by intracytoplasmic inclusions called Lewy bodies (LB) and degeneration of dopaminergic neurons in the substantia nigra (SN). Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several proteins and organelles. Galectin-3 (GAL3) is known to have a detrimental function in neurodegenerative diseases. It is a galactose-binding protein without known catalytic activity and is expressed mainly by activated microglial cells in the central nervous system (CNS). GAL3 has been previously found in the outer layer of the LB in post-mortem brains. However, the role of GAL3 in PD is yet to be elucidated. In post-mortem samples, we identified an association between GAL3 and LB in all the PD subjects studied. GAL3 was linked to less αSYN in the LB outer layer and other αSYN deposits, including pale bodies. GAL3 was also associated with disrupted lysosomes. In vitro studies demonstrate that exogenous recombinant Gal3 is internalised by neuronal cell lines and primary neurons where it interacts with endogenous αSyn fibrils. In addition, aggregation experiments show that Gal3 affects spatial propagation and the stability of pre-formed αSyn fibrils resulting in short, amorphous toxic strains. To further investigate these observations in vivo, we take advantage of WT and Gal3KO mice subjected to intranigral injection of adenovirus overexpressing human αSyn as a PD model. In line with our in vitro studies, under these conditions, genetic deletion of GAL3 leads to increased intracellular αSyn accumulation within dopaminergic neurons and remarkably preserved dopaminergic integrity and motor function. Overall, our data suggest a prominent role for GAL3 in the aggregation process of αSYN and LB formation, leading to the production of short species to the detriment of larger strains which triggers neuronal degeneration in a mouse model of PD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Galectin-3 (GAL3)
- Lewy body (LB)
- Parkinson’s disease (PD)
- α-synuclein (αSYN)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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García-Revilla, ...
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Boza-Serrano, An ...
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Jin, Yiyun
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Vadukul, Devkee ...
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Soldán-Hidalgo, ...
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Camprubí-Ferrer, ...
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García-Cruzado, ...
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Martinsson, Isak
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Klementieva, Oxa ...
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Ruiz, Rocío
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Aprile, Francesc ...
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Deierborg, Tomas
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Venero, José Lui ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Acta Neuropathol ...
- Av lärosätet
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Lunds universitet