Asset Details
Do you wish to reserve the book?
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis
Do you wish to request the book?
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis
2019
Overview
In Parkinson’s disease (PD) there is a selective degeneration of neuromelanin-containing neurons, especially substantia nigra dopaminergic neurons. In humans, neuromelanin accumulates with age, the latter being the main risk factor for PD. The contribution of neuromelanin to PD pathogenesis remains unknown because, unlike humans, common laboratory animals lack neuromelanin. Synthesis of peripheral melanins is mediated by tyrosinase, an enzyme also present at low levels in the brain. Here we report that overexpression of human tyrosinase in rat substantia nigra results in age-dependent production of human-like neuromelanin within nigral dopaminergic neurons, up to levels reached in elderly humans. In these animals, intracellular neuromelanin accumulation above a specific threshold is associated to an age-dependent PD phenotype, including hypokinesia, Lewy body-like formation and nigrostriatal neurodegeneration. Enhancing lysosomal proteostasis reduces intracellular neuromelanin and prevents neurodegeneration in tyrosinase-overexpressing animals. Our results suggest that intracellular neuromelanin levels may set the threshold for the initiation of PD.
It is unclear if neuromelanin plays a role in Parkinson’s disease pathogenesis since common laboratory animals lack this pigment. Authors show here that overexpression of human tyrosinase in the substantia nigra of rats resulted in an age-dependent production of human-like neuromelanin within nigral dopaminergic neurons and is associated with a Parkinson’s disease phenotype when allowed to accumulate above a specific threshold.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 101/58
/ 13
/ 13/51
/ 14
/ 14/19
/ 14/63
/ 38
/ 38/77
/ 42
/ 42/44
/ 59
/ 59/57
/ 64
/ 64/60
/ 64/86
/ 96
/ 96/106
/ 96/109
/ 96/31
/ Age
/ alpha-Synuclein - deficiency
/ alpha-Synuclein - metabolism
/ Animals
/ Brain
/ Dopaminergic Neurons - metabolism
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Monophenol Monooxygenase - genetics
/ Monophenol Monooxygenase - metabolism
/ Neurons
/ Parkinson Disease - genetics
/ Parkinson Disease - metabolism
/ Parkinson Disease - pathology
/ Parkinsonian Disorders - genetics
/ Parkinsonian Disorders - metabolism
/ Parkinsonian Disorders - pathology
/ Rats
/ Recombinant Proteins - genetics
/ Recombinant Proteins - metabolism
/ Science
