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Research Breakthroughs

A kinase that restores memory and cognitive defects in a mouse model of Alzheimer's disease discovered

In an exciting study published in the journal Neuron, Drs. Huda Zoghbi and Juan Botas have identified a kinase whose partial inhibition reduced aberrant tau aggregates and reversed memory deficits in a mouse model of neurodegeneration. In this study, researchers employed an innovative approach to identify novel genetic modifiers of tauopathy. They performed a stringent parallel cross-species screen of approximately 600 known kinases in a human cell line and fruit flies that overexpressed tau.

A novel role for the basal forebrain in regulating appetite

A seminal study published in Nature from the laboratory of Dr. Benjamin Arenkiel, associate professor at Baylor College of Medicine and researcher at the Neurological Research Institute at Texas Children's Hospital, demonstrates that a subset of cholinergic neurons in the basal forebrain act as critical regulators to modulate food intake and control body weight.

Deep brain stimulation can correct neural malfunction in Rett and MeCP2 duplication syndrome mice

A paper published this week in Neuron from Dr. Huda Y. Zoghbi’s laboratory shows that identical abnormalities in neural circuits might underlie similar features in two distinct genetic syndromes – Rett syndrome and MECP2 duplication syndrome. It was even more exciting that deep brain stimulation (DBS) reversed these circuit malfunctions in mouse models of Rett syndrome.

Loss of Frataxin causes neurodegeneration due to iron toxicity

A recent study published in the journal eLife by Dr. Hugo J. Bellen’s team at Baylor College of Medicine and Neurological Research Institute at Texas Children’s Hospital has provided the first experimental evidence that loss of frataxin may cause neurodegeneration via iron toxicity.

NRI researchers develop a rat model of Rett Syndrome

A team of researchers at the NRI led by Dr. Rodney Samaco characterized a novel genetic rat model of RTT that closely mimics many behavioral and molecular features of RTT patients. This study was published last week in the Human Molecular Genetics journal, with Dr. Surabi Veeraragavan. After confirming the rat model of RTT was missing the MeCP2 protein, the researchers set out to test the behavior of the animals, focusing on female rats.

Reducing MeCP2 levels reverses MeCP2 duplication syndrome

In 2004 a team of researchers led by Dr. Huda Zoghbi, director of NRI and professor of molecular and human genetics at the Baylor College of Medicine, developed a mouse model for this duplication syndrome and hypothesized that excessive levels of MECP2 is the cause of the neurological symptoms observed in these patients. A year later the first individuals with duplication syndrome were diagnosed.

Deep brain stimulation restores learning and memory in Rett Syndrome mice

In a recent study published in Nature, a team of researchers have demonstrated that DBS of a specific area of the brain can revert learning and memory deficits in a mouse model of Rett syndrome, a leading cause of intellectual disability in girls. Although DBS has shown some promise in many movement disorders and neuropsychiatric disorders in children, this is the first experimental demonstration of the effectiveness of DBS in treating a childhood cognitive disorder.

USP7: A deubiquinating enzyme implicated in neurodevelopmental disorders

In a recent study published in Molecular Cell3, researchers have identified a novel role for Ubiquitin-specific peptidase 7 (USP7), a deubiquitinating enzyme, in PWS, Schaaf-Yang syndrome and a hitherto unidentified neurological disease. The authors initiated this study to identify interacting partners of MAGEL2-TRIM27 and were surprised to isolate a deubiquinating enzyme, USP7 as one of the interactors.

Insufficient energy production by mitochondria causes photoreceptor neurons to degenerate

It is thought that mitochondrial defects result in elevated levels of oxidative stress, which is the primary cause of disease progression. However, contrary to this established paradigm, a recent study from Dr. Hugo Bellen’s team shows that mutations in some genes that affect mitochondrial ATP production cause neuronal degeneration independent of oxidative stress.

Neuronal hyperactivity accelerates the loss of neural stem cells

An exciting study from the laboratories of Drs. Mirjana Maletic-Savatic and Juan Manuel Encinas, published in Cell Stem Cell, sheds light on how neuronal activity affects rNSC division and thereby, generation of new neurons in adults. They demonstrated that excessive neuronal activity results in the loss of rNSCs and thereby, affects short-term as well as long-term generation of new neurons in adult hippocampus.

Starvation and exercise stimulate autophagy via a novel lysosomal signaling mechanism

In a recent study published in Nature Cell Biology, NRI researcher, Andrea Ballabio’s team has shown how starvation and exercise triggers a novel lysosomal calcium signaling cascade leading to transcriptional activation of the autophagic/lysosomal pathway. They found that under normal feeding conditions, mTORC1 kinase present on the lysosomal surface phosphorylates transcription factor B (TFEB), rendering it inactive. This form of TFEB can bind to 14-3-3 proteins that allows it to remain sequestered in the cytoplasm.

Chicken and mice models shed light on how to repair human neonatal brain injury

An exciting study published in Neuron from the laboratory of Dr. Benjamin Deneen has identified a novel mechanism that regulates formation of OLs via Wnt signalosomes. More importantly, it has identified a promising Wnt regulator that is capable of stimulating remyelination in animal models of cerebral palsy and adult white matter injury.

Voltage-gated calcium channels regulate autophagy in neurons

A recent study published in PLoS Biology, by a research team led by Drs. Chao Tong and Hugo Bellen has identified a novel mechanism by which neurons regulate autophagy. Autophagy is an evolutionarily conserved and tightly regulated cellular quality control process. It is an essential function that occurs in most cells to remove damaged organelles or misfolded proteins.

Fruit fly research paves the way for biomedical discoveries

Baylor College of Medicine faculty and fruit fly biologists at the NRI, Drs. Michael Wangler, Shinya Yamamoto and Hugo J Bellen have published an article this week titled, “Fruit flies in Biomedical Research“, in the journal Genetics that explores the value of fruit fly research in biomedical discoveries and the need for additional funding. This insightful article provides an excellent summary of some of the key contributions resulting from a century of using fruit flies for biomedical research.

Researchers discover how mitochondrial fusion regulates neuromuscular junction synapse development

While it is known that defects in mitochondrial transport or dynamics in neurons result in neurological or neurodegenerative diseases, it is not clear what the underlying causative steps are. For instance, while it was known that loss of mitochondrial fusion protein, Mitofusin 2 (Mfn2) causes Charcot Marie Tooth type 2A (CMT2A), a progressive and severe loss of motor neurons, the mechanism by which functional loss of Mfn2 result in neuropathy is not clear. A recent paper from Dr. Hugo Bellen’s lab provides a clue.

Hippocampal place cells create a simple topological template to represent spatial information

A pioneering study published this month in eLife by Dr. Yuri Dabaghian and his colleagues at the NRI and the University of California at San Francisco, suggests the existence of a simpler, yet elegant mechanism. They show that place cells ignore all extraneous geometric information and merely convey a “rough and ready” topological map of the environment. In other words, the hippocampal map consists merely of a sequence of spatial locations, analogous to a city's subway map.

A novel neuropeptide signaling integrates adult-born neurons into existing circuitries

This week, in Developmental Cell, Dr. Arenkiel and his team report a novel role for a small, soluble neuropeptide, Corticotrophin Release Hormone (CRH) in promoting synapse formation and circuit integration of neurons generated in the adult mouse brain. Traditionally, CRH has been studied as a hypothalamic stress hormone. However, it is now known that CRH is released by various neurons throughout the brain.

Mutation location is the key to prognosis

The three most important factors in real estate are location, location, location, and the same might be said for mutations in the gene MECP2, said researchers in a report in the journal Cell. In the study, the researchers relied on data from rare male patients with disruptions in MECP2 that showed that severity of symptoms could be influenced by the location of the gene mutation.

MicroRNA helps unravel the mystery of the Rett protein, MeCP2

A snippet of genetic material called microRNA provides new insight into the control of the protein MeCP2, which causes disease when there is too much or too little of it in the brain, said researchers in a report in the journal Genes and Development. In this report, Dr. Zoghbi and her colleagues describe a microRNA known as miR-483-5p that plays an important role in regulating the levels of MeCP2 protein in the fetal brain during development.