E-viri
Recenzirano
Odprti dostop
-
MacLeod, David A.; Rhinn, Herve; Kuwahara, Tomoki; Zolin, Ari; Di Paolo, Gilbert; McCabe, Brian D.; Marder, Karen S.; Honig, Lawrence S.; Clark, Lorraine N.; Small, Scott A.; Abeliovich, Asa
Neuron (Cambridge, Mass.), 02/2013, Letnik: 77, Številka: 3Journal Article
Recent genome-wide association studies have linked common variants in the human genome to Parkinson’s disease (PD) risk. Here we show that the consequences of variants at 2 such loci, PARK16 and LRRK2, are highly interrelated, both in terms of their broad impacts on human brain transcriptomes of unaffected carriers, and in terms of their associations with PD risk. Deficiency of the PARK16 locus gene RAB7L1 in primary rodent neurons, or of a RAB7L1 ortholog in Drosophila dopamine neurons, recapitulated degeneration observed with expression of a familial PD mutant form of LRRK2, whereas RAB7L1 overexpression rescued the LRRK2 mutant phenotypes. PD-associated defects in RAB7L1 or LRRK2 led to endolysosomal and Golgi apparatus sorting defects and deficiency of the VPS35 component of the retromer complex. Expression of wild-type VPS35, but not a familial PD-associated mutant form, rescued these defects. Taken together, these studies implicate retromer and lysosomal pathway alterations in PD risk. ► Genetic variants at PARK16 and LRRK2 interact to modify Parkinson’s disease risk ► Splicing of the PARK16 locus gene RAB7L1 is modified by genetic variants ► RAB7L1 and LRRK2 coordinately regulate protein sorting through the retromer pathway ► Expression of the retromer component VPS35 can suppress LRRK2 mutant pathology MacLeod et al. combine innovative human functional genomics approaches with cell and animal model studies to provide convergent evidence that links three Parkinson’s disease-associated genes—RAB7L1, PARK16, and VPS35—to defective protein sorting through the retromer pathway and neurodegeneration.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.