Huntington's disease is caused by a polyglutamine expansion in the huntingtin (htt) protein, and previous data indicate that over-activation of NMDA receptors (NMDARs) may be involved in the selective degeneration of cells expressing NR1/NR2B NMDARs. We used Kinetworkstrade mark multi-immunoblotting screens to examine expression of 76 protein kinases, 18 protein phosphatases, 25 heat shock/stress proteins, and 27 apoptosis proteins in human embryonic kidney 293 cells transfected with NR1/NR2B and htt containing 15 (htt-15Q; wild-type) or 138 (htt-138Q; mutant) glutamine repeats. Follow-up experiments revealed several proteins involved in the heat-shock response pathway to be up-regulated in the soluble fraction from cells expressing htt-138Q, including protein phosphatase 5 and cyclin-dependent kinase 5. Increased expression in the soluble fraction of htt-138Q-expressing cells was also noted for the stress- and calcium-activated protein-serine/threonine kinase casein kinase 2, a change which was confirmed in striatal tissue of yeast artificial chromosome transgenic mice expressing full-length mutant htt. Inhibition of casein kinase 2 activity in cultured striatal neurons from these mice significantly exacerbated NMDAR-mediated toxicity, as assessed by labeling of apoptotic nuclei. Our findings are consistent with up-regulation of components of the stress response pathway in the presence of polyglutamine-expanded htt and NR1/NR2B which may reflect an attempt at the cellular level to ameliorate the detrimental effects of mutant htt expression.
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http://dx.doi.org/10.1111/j.1471-4159.2007.05016.x | DOI Listing |
Cureus
December 2024
Clinical Research, National Institute of Neurology and Neurosurgery, Mexico City, MEX.
Anti-NMDA (N-methyl-D-aspartate) receptor encephalitis (ANRE) is a rare autoimmune condition targeting brain receptors, often linked to ovarian tumors in young women. In severe cases, it can lead to status epilepticus, but in sporadic cases, it may progress to super-refractory status epilepticus (SRSE), a dangerous state of continuous or repetitive seizures demanding urgent medical attention that continues or recurs more than 24 hours after the initiation of anesthetic therapy. We present a case report of anti-NMDA receptor limbic encephalitis-triggered SRSE terminated with vagus nerve stimulation (VNS) and titrated to high stimulation parameters in the immediate postoperative period.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Neurology, Huashan Hospital, Fudan University and Institute of Neurology, Fudan University, Shanghai, China.
We report a case of optic neuritis (ON) secondary to autoimmune encephalitis (AE) in a patient with concomitant antibodies to N-methyl-D-aspartate receptor (NMDAR), gamma-aminobutyric acid-B receptor (GABAR), and myelin oligodendrocyte glycoprotein (MOG). The patient exhibited a constellation of symptoms, including vision loss, seizures, mental and behavioral disorders, cognitive impairment, and speech abnormalities. At the two-year follow-up, the patient's symptoms had abated entirely.
View Article and Find Full Text PDFBiochem Soc Trans
January 2025
Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud-sección Medicina, Universidad de La Laguna, Tenerife, ES-38071, Spain.
Large conductance voltage- and calcium-activated potassium channels (BK channels) are extensively found throughout the central nervous system and play a crucial role in various neuronal functions. These channels are activated by a combination of cell membrane depolarisation and an increase in intracellular calcium concentration, provided by calcium sources located close to BK. In 2001, Isaacson and Murphy first demonstrated the coupling of BK channels with N-methyl-D-aspartate receptors (NMDAR) in olfactory bulb neurons.
View Article and Find Full Text PDFBiol Psychiatry
January 2025
Institute of Biology Paris-Seine, laboratory Neuroscience Paris-Seine, CNRS, INSERM, Sorbonne Université, UPMC Université Paris 06 F-75005, Paris, France. Electronic address:
Background: The persistence of cocaine-evoked adaptations relies on gene regulations within the reward circuit, especially in the ventral striatum (i.e., nucleus accumbens (NAc)).
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Pathology, Faculty of Health Care and Social Work, Trnava University and University Hospital, 917 02 Trnava, Slovakia.
The autoantibodies against the NR1 subunit are well known in the pathomechanism of NMDAR encephalitis. The dysfunction of the NR2 subunit could be a critical factor in this neurological disorder due to its important role in the postsynaptic pathways that direct synaptic plasticity. We report a case of paraneoplastic anti-NMDAR encephalitis presented alongside very severe illness.
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