Subhojit Roy on Does Oleic Acid Hold the Key to α-Synuclein Toxicity?

COMMENT These are exciting findings, with implications for α-synuclein therapeutics and Parkinson's disease. Researchers have known that α-synuclein interacts with lipids for some time, but few therapeutic strategies have exploited this property. The two ...

Subhojit Roy on Sans Synuclein Tetramers, Mice Mimic Parkinson’s Disease

COMMENT This study by Silke Nuber, Ulf Dettmer, Dennis Selkoe and colleagues explores a key idea that they have championed—that α-syn normally exists as a multimer/tetramer, but abrogation of these physiologic conformations leads to an increase in monomers, ...

Subhojit Roy on CRISPR Gene Editing May Not Be so Precise After All

COMMENT This data from Allan Bradley and colleagues suggest there could be problems using CRISPRs in dividing cells, because the authors found large deletions and more complex genomic rearrangements at targeted sites. Though it has been long recognized that ...

Jichao Sun, Subhojit Roy on Antisense Oligonucleotides Turn Down the Aβ Spigot

COMMENT This is a very interesting study by Jennifer Chang, Michelle Hastings and colleagues, targeting APP using splice-switching antisense oligonucleotides. Traditionally, the field has focused on developing small molecule inhibitors of BACE; and although the ...

Subhojit Roy on Close Encounters: A New Look at Where APP and BACE1 Meet

COMMENT We thank our colleagues for taking the time to read our paper and comment. Dr. Almeida's points are well taken; it is possible that there is some interference of normal trafficking after complementation (as we pointed out in the manuscript and in our ...

Subhojit Roy on Presynaptic alpha-synuclein aggregation in a mouse model of Parkinson's disease.

COMMENT These studies from Vivek Unni’s lab reiterate the importance of focusing on the synaptic accumulation and aggregation of α-synuclein, rather than somatic Lewy bodies. Specifically, they strengthen the hypothesis that small increments in α-synuclein are ...

Subhojit Roy on A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies.

COMMENT This study confirms links between dementia with Lewy bodies (DLB) and glucocerebrosidase (GBA) mutations, expanding on several other studies that have shown links between GBA and Parkinson's disease (PD)/DLB. The strengths of this study are its ...

Subhojit Roy on α-Syn suppression reverses synaptic and memory defects in a mouse model of dementia with Lewy bodies.

COMMENT Deciphering details of α-synuclein-induced pathology in the brain has been surprisingly challenging, and the data by Lim et al., 2011, using an inducible system driven by the CamKII-promoter offer significant insights. While there are many notable take ...

Subhojit Roy on Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies.

COMMENT Nice study by Mazzuli et al. linking glucocerebrosides to α-synuclein. s1roy 0 ...

Subhojit Roy on Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice.

COMMENT Wonderful, rigorous study, and perhaps a window into the future of neurodegeneration research. Though the thought is slightly disturbing, it is becoming more and more apparent that the aggregates, plaques, and tangles that we neuropathologists love to see ...

Subhojit Roy on α-Synuclein’s Day Job: To Chaperone SNARE Complexes?

COMMENT By directly examining SNARE assembly, Burre et al. present good evidence that α-synuclein plays a role in facilitating the assembly of SNARE complexes. They also show that this facilitating process depends on synaptic activity and propose that the ...

Subhojit Roy on Excess α-Synuclein Sends Synapses Sputtering

COMMENT Our goal in this study was to try connecting the dots between two key pathologic events: modestly elevated α-synuclein levels within the neuron and the ultimate synaptic dysfunction. We used a cell-biological approach that allowed us to analyze and ...

Subhojit Roy on The Many Misdeeds of Aβ—Seizures and Axonal Transport Interference

COMMENT The study by Pigino et al. study elegantly highlights a possible mechanism by which Aβ oligomers can influence axonal transport. Though the validity of intracellular Aβ is debatable in the context of human AD pathology, Pigino et al. convincingly show ...

Subhojit Roy on Paris: Intracellular Traffic and Neurodegenerative Disorders

COMMENT This article reiterates the critical importance of studying AD in the context of the neuron/brain as a whole, and also underlines the fact that the neuron is different from every other cell in our body. s1roy 0 ...

Subhojit Roy on Dopaminergic Transplants—Stable But Prone to Parkinson’s?

COMMENT These studies elegantly demonstrate that transplanted fetal grafts can survive and thrive in human brains for prolonged periods, clearly moving the field in new, exciting directions. However, the view that the presence of α-synuclein in these grafted ...