Bhuvaneish T. Selvaraj
YOU?
Author Swipe
View article: Syntaphilin loss enhances mitochondrial axonal transport and neuromuscular junction formation in a human stem cell derived neuromuscular assembloid model
Syntaphilin loss enhances mitochondrial axonal transport and neuromuscular junction formation in a human stem cell derived neuromuscular assembloid model Open
Background The neuromuscular junction (NMJ) is the synapse between motor neurons and skeletal muscle and controlls movement. Impaired synaptic transmission and NMJ degeneration has been observed during healthy ageing and is also implicated…
View article: A multimodal screening platform for endogenous dipeptide repeat proteins in C9orf72 patient iPSC neurons
A multimodal screening platform for endogenous dipeptide repeat proteins in C9orf72 patient iPSC neurons Open
Repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia. Repeat-associated non-AUG (RAN) translation generates neurotoxic dipeptide repeat proteins (DPRs). To study endogenous DPR…
View article: Systematic Living Evidence for Clinical Trials (SyLECT): a data-driven framework for drug selection in clinical trials in motor neuron disease
Systematic Living Evidence for Clinical Trials (SyLECT): a data-driven framework for drug selection in clinical trials in motor neuron disease Open
Despite many promising preclinical studies and decades of clinical trials, there remains a paucity of effective disease-modifying drugs in motor neuron disease. We aimed to develop a systematic and structured data-driven framework to ident…
View article: The Fragile X Messenger Ribonucleoprotein 1 Regulates the Morphology and Maturation of Human and Rat Oligodendrocytes
The Fragile X Messenger Ribonucleoprotein 1 Regulates the Morphology and Maturation of Human and Rat Oligodendrocytes Open
The Fragile X Messenger Ribonucleoprotein (FMRP) is an RNA binding protein that regulates the translation of multiple mRNAs and is expressed by neurons and glia in the mammalian brain. Loss of FMRP leads to fragile X syndrome (FXS), a comm…
View article: Role of glia in delirium: proposed mechanisms and translational implications
Role of glia in delirium: proposed mechanisms and translational implications Open
View article: Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy
Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy Open
Increasing evidence suggests an essential function for autophagy in unconventional protein secretion (UPS). However, despite its relevance for the secretion of aggregate-prone proteins, the mechanisms of secretory autophagy in neurons have…
View article: Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial
Safety and efficacy of memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial Open
The Euan MacDonald Centre, MND Scotland, My Name'5 Doddie Foundation, and Baillie Gifford.
View article: The Fragile X Messenger Ribonucleoprotein 1 regulates the morphology and maturation of human and rat oligodendrocytes
The Fragile X Messenger Ribonucleoprotein 1 regulates the morphology and maturation of human and rat oligodendrocytes Open
The Fragile X Messenger Ribonucleoprotein (FMRP) is an RNA binding protein that regulates the translation of multiple mRNAs and is expressed by neurons and glia in the mammalian brain. Loss of FMRP leads to Fragile X Syndrome (FXS), a comm…
View article: Human induced pluripotent stem cell-derived microglia contribute to the pathophysiology of Fragile X syndrome via increased RAC1 signaling
Human induced pluripotent stem cell-derived microglia contribute to the pathophysiology of Fragile X syndrome via increased RAC1 signaling Open
Fragile X syndrome (FXS) is one of the most common monogenic causes of neurodevelopmental disorders characterized by intellectual disability, autism and epilepsy. Emerging evidence suggests a role for immune dysfunction in autism. Using in…
View article: Neuronal Circuit Dysfunction in Amyotrophic Lateral Sclerosis
Neuronal Circuit Dysfunction in Amyotrophic Lateral Sclerosis Open
The primary neural circuit affected in Amyotrophic Lateral Sclerosis (ALS) patients is the corticospinal motor circuit, originating in upper motor neurons (UMNs) in the cerebral motor cortex which descend to synapse with the lower motor ne…
View article: Cell-autonomous immune dysfunction driven by disrupted autophagy in <i>C9orf72</i> -ALS iPSC-derived microglia contributes to neurodegeneration
Cell-autonomous immune dysfunction driven by disrupted autophagy in <i>C9orf72</i> -ALS iPSC-derived microglia contributes to neurodegeneration Open
Although microglial activation is widely found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the underlying mechanism(s) are poorly understood. Here, using human-induced pluripotent stem cell–derived microglia-l…
View article: Astrocytes mediate cell non-autonomous correction of aberrant firing in human FXS neurons
Astrocytes mediate cell non-autonomous correction of aberrant firing in human FXS neurons Open
View article: A 3D cell culture system for bioengineering human neuromuscular junctions to model ALS
A 3D cell culture system for bioengineering human neuromuscular junctions to model ALS Open
The signals that coordinate and control movement in vertebrates are transmitted from motoneurons (MNs) to their target muscle cells at neuromuscular junctions (NMJs). Human NMJs display unique structural and physiological features, which m…
View article: Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus
Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus Open
Objectives Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a syste…
View article: Blood-CNS barrier dysfunction in amyotrophic lateral sclerosis: Proposed mechanisms and clinical implications
Blood-CNS barrier dysfunction in amyotrophic lateral sclerosis: Proposed mechanisms and clinical implications Open
There is strong evidence for blood-brain and blood-spinal cord barrier dysfunction at the early stages of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Since impairment of the blood-central nervous system …
View article: PolyGA targets the ER stress-adaptive response by impairing GRP75 function at the MAM in C9ORF72-ALS/FTD
PolyGA targets the ER stress-adaptive response by impairing GRP75 function at the MAM in C9ORF72-ALS/FTD Open
ER stress signaling is linked to the pathophysiological and clinical disease manifestations in amyotrophic lateral sclerosis (ALS). Here, we have investigated ER stress-induced adaptive mechanisms in C9ORF72 -ALS/FTD, focusing on uncoverin…
View article: Mitochondrial bioenergetic dysfunction and cryptic splicing of stathmin-2 are neuropathological markers of disease duration in sporadic amyotrophic lateral sclerosis
Mitochondrial bioenergetic dysfunction and cryptic splicing of stathmin-2 are neuropathological markers of disease duration in sporadic amyotrophic lateral sclerosis Open
A striking feature of sporadic amyotrophic lateral sclerosis (ALS) is the marked heterogeneity in disease duration; despite the stark median survival of three years from symptom onset, 10-20% of people with ALS survive longer than 10 years…
View article: HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS
HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS Open
View article: Cell-autonomous immune dysfunction driven by disrupted autophagy in <i>C9orf72</i>-ALS iPSC-derived microglia contributes to neurodegeneration
Cell-autonomous immune dysfunction driven by disrupted autophagy in <i>C9orf72</i>-ALS iPSC-derived microglia contributes to neurodegeneration Open
The most common genetic mutation found in familial and sporadic amyotrophic lateral sclerosis (ALS), as well as fronto-temporal dementia (FTD), is a repeat expansion in the C9orf72 gene. C9orf72 is highly expressed in human myeloid cells, …
View article: The ciliary gene INPP5E confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic hedgehog signaling
The ciliary gene INPP5E confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic hedgehog signaling Open
View article: A Systematic Approach to Identify Neuroprotective Interventions for Motor Neuron Disease
A Systematic Approach to Identify Neuroprotective Interventions for Motor Neuron Disease Open
Background Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Objectives Here we deta…
View article: Assessment of Mitochondrial Trafficking as a Surrogate for Fast Axonal Transport in Human Induced Pluripotent Stem Cell–Derived Spinal Motor Neurons
Assessment of Mitochondrial Trafficking as a Surrogate for Fast Axonal Transport in Human Induced Pluripotent Stem Cell–Derived Spinal Motor Neurons Open
View article: iPSC-derived myelinoids to study myelin biology of humans
iPSC-derived myelinoids to study myelin biology of humans Open
View article: TDP-43 proteinopathy in oligodendrocytes revealed using an induced pluripotent stem cell model
TDP-43 proteinopathy in oligodendrocytes revealed using an induced pluripotent stem cell model Open
Oligodendrocytes are implicated in Amytrophic Lateral Sclerosis pathogenesis and display TDP-43 pathological inclusions. To investigate the cell autonomous consequences of TDP-43 mutations on human oligodendrocytes, we generated oligodendr…
View article: Dysregulation in Subcellular Localization of Myelin Basic Protein mRNA Does Not Result in Altered Myelination in Amyotrophic Lateral Sclerosis
Dysregulation in Subcellular Localization of Myelin Basic Protein mRNA Does Not Result in Altered Myelination in Amyotrophic Lateral Sclerosis Open
Pathological hallmarks of amyotrophic lateral sclerosis (ALS), including protein misfolding, are well established in oligodendrocytes. More recently, an RNA trafficking deficit of key myelin proteins has been suggested in oligodendrocytes …
View article: The ciliary gene <i>INPP5E</i> confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic Hedgehog signalling
The ciliary gene <i>INPP5E</i> confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic Hedgehog signalling Open
SUMMARY Defects in primary cilia, cellular antennas that controls multiple intracellular signalling pathways, underlie several neurodevelopmental disorders, but how cilia control essential steps in human brain formation remains elusive. He…
View article: iPSC-derived myelinoids to study myelin biology of humans
iPSC-derived myelinoids to study myelin biology of humans Open
View article: <i>C9orf72</i> -derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility
<i>C9orf72</i> -derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility Open
Arginine-rich dipeptide repeats associated with ALS and FTD inhibit machinery for microtubule-based axonal cargo transport.
View article: 40 Years of CSF Toxicity Studies in ALS: What Have We Learnt About ALS Pathophysiology?
40 Years of CSF Toxicity Studies in ALS: What Have We Learnt About ALS Pathophysiology? Open
Based on early evidence of in vitro neurotoxicity following exposure to serum derived from patients with amyotrophic lateral sclerosis (ALS), several studies have attempted to explore whether cerebrospinal fluid (CSF) obtained from people …
View article: Altered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction
Altered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction Open