51 RESULTS
COMMENT There is increasing evidence that there are aggregated forms of α-synuclein throughout many tissues that arise during disease evolution in Parkinson’s disease (PD) and related movement disorders, such as MSA. For example, several groups have now reliably
COMMENT This report pairs of IPSC neurons where LRRK2 mutation status associates with a shift in the tetramer-monomer ratio in neurons and an increase in pS129-synuclein. This latter observation is particularly interesting as the assay for measuring pS129-synucle
COMMENT The report by Hu et al. suggesting that TMEM175, a risk gene for PD, is a lysosomal proton channel is quite striking in the context of prior claims of activity encoded by this channel. For example, work from Wie et al. (Wie et al., 2021) last year reporte
COMMENT This paper is an impressive application of two types of single-cell analysis, especially when considering the additional flow sorting step to enrich for dopamine neurons in figure 1. That the general dorsal/ventral gradient of calbindin vs. SOX6 is replic
COMMENT Finding ways to image α-synuclein pathology in the human brain is a critical need in the neurodegenerative field, as this could allow for both evaluation of disease progression and, potentially, for differential diagnosis between diseases. For example, co
COMMENT This technique is very interesting and could be more widely applied across neurodegenerative diseases. In particular, it would be really interesting to see which changes in disease are specific to AD, and which are due to damaged synapses reacting to dise
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 additiona
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, s
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 fro
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 es
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 exp
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 uptak
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
