45 RESULTS
COMMENT The paper by Mertens et al. identifies an important approach to using human cells in the context of both sporadic and familial AD. One especially intriguing possibility would be to identify specific age-related pathways that the fibroblast-derived neurons ...
COMMENT These two papers substantially increase our structural knowledge of LRRK2, which to date has largely been based on small fragments of the protein. Identifying potential structures in situ is particularly helpful and improving the resolution with ...
COMMENT The overall collection of gnomAD papers is an important resource for the field. That the underlying data is in the public domain is really important—it’s a common first stop to evaluate whether disease variants are rare and more likely to be pathogenic, ...
COMMENT As the authors indicate, this has important implications for lab modelling of synucleinopathies. It would seem relatively important to be able to show whether the types of assemblies we use in the lab are at all related structurally to those extracted ...
COMMENT These two papers nicely complement each other in saying that lysosomal dysfunction and accumulation of α-synuclein are related, and are a potentially tractable therapy for PD. However, the two papers take different mechanistic approaches and therefore are ...
COMMENT The work from Joshi et al. provides an interesting mechanistic hypothesis to explain how multiple cell types may contribute to several different neurodegenerative diseases. That non-neuronal cells contribute to neuronal cell loss probably has been best ...
COMMENT The work from Fecher et al. is a very innovative solution to the older problem of estimating if mitochondria in major cell types of the mammalian brain are different. Based on their differing physiology and energetic requirements, it is gratifying, if ...
COMMENT This work by Gerez et al. helps us fill out the molecular machinery that controls uptake and degradation of α-synuclein from the extracellular space. Consistent with other literature, the authors seem to see a signature around endosomal pathways for ...
COMMENT Classifying gene-expression patterns and their relationship to genetic variants is a very important way to determine proximate genetic mechanisms arising from genome-wide association studies (GWAS). The use of laser capture microdissection and RNA-seq is ...
COMMENT The current set of GWAS-related studies indicates that there are still significant loci to find for Alzheimer’s disease, and likely for other neurodegenerative conditions, as sample sizes increase. By definition, these will be loci with smaller effect ...
COMMENT The paper by Richarme and colleagues suggests that DJ-1 can repair glycated nucleotides, derived from either RNA or DNA, in addition to the previously claimed removal of glycation products from proteins. Thus, DJ-1 homologues would be the only extant ...
COMMENT The paper by Szelechowski et al. is very interesting and another example of how studying viruses can lead to insights into broader biological processes. I find it intriguing that viruses that are dormant in neurons might protect their cellular hosts by ...
COMMENT The key thing these authors show in this paper, and this is why it is an important study, is that Fbxo7 mutations interact with an established pathway for recessive parkinsonism. The authors clearly show that the mutations are loss of function, which is ...
COMMENT This paper by Chan et al. develops the previous reports of an effect of LRRK2 on neurite length to include a specific molecular effector, Rac1. That LRRK2 influences neurite length in cell culture is reasonably well established, as several labs have ...
COMMENT This study by Lin et al. provides an excellent opportunity to reevaluate the proposed role of LRRK2 on neurite outgrowth and maintenance. Work from the Abeliovich lab first showed that LRRK2, and especially mutant LRRK2, can limit the outgrowth of ...
