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Huntington's disease (HD), a genetic neurodegenerative disease caused by a polyglutamine expansion in the Huntingtin (Htt) protein, is accompanied by multiple mitochondrial alterations. Here, we show that mitochondrial fragmentation and cristae alterations characterize cellular models of HD and participate in their increased susceptibility to apoptosis. In(More)
The DSCR1 (Adapt78) gene was independently discovered as a resident of the "Down syndrome candidate region"and as an "adaptive response"shock or stress gene that is transiently induced during oxidative stress. Recently the DSCR1 (Adapt78) gene product was discovered to be an inhibitor of the serine/threonine phosphatase, calcineurin, and its signaling(More)
Amyloid-β peptide (Aβ) toxicity and tau hyperphosphorylation are hallmarks of Alzheimer's disease (AD). How their molecular relationships may affect the etiology, progression, and severity of the disease, however, has not been elucidated. We now report that incubation of fetal rat cortical neurons with Aβ upregulates expression of the Regulator of(More)
DSCR1(Adapt78) is a stress responsive gene that can be induced by multiple stresses. We have previously demonstrated that acute DSCR1(Adapt78) overexpression can transiently protect cells against oxidative stress and calcium-mediated stresses, while its chronic overexpression is associated with neurofibrillary tangles, Alzheimer disease, and Down's(More)
Hyperphosphorylated tau proteins accumulate in the paired helical filaments of neurofibrillary tangles seen in such tauopathies as Alzheimer's disease. In the present paper we show that tau turnover is dependent on degradation by the proteasome (inhibited by MG132) in HT22 neuronal cells. Recombinant human tau was rapidly degraded by the 20 S proteasome in(More)
We have confirmed the expression of CRH and CRH receptor type 1 genes in human skin, cultured HaCaT keratinocytes, squamous cell carcinoma, and melanoma cells. The size of CRH messenger ribonucleic acid (mRNA), estimated by Northern blot hybridization, was 1.5 kilobases. CRH peptide was identified by reverse phase high pressure liquid chromatography(More)
At least two different isoforms of RCAN1 mRNA are expressed in neuronal cells in normal human brain. Although RCAN1 mRNA is elevated in brain regions affected by Alzheimer's disease, it is not known whether the disease affects neuronal RCAN1, or if other cell types (e.g. astrocytes or microglia) are affected. It is also unknown how many protein isoforms are(More)
INTRODUCTION AND SIGNIFICANCE The serine-threonine phosphatase, calcineurin (also known as PP3C, formerly PP2B) plays pivotal roles in a wide series of key biological processes. A new family of regulators of calcineurin (RCANs) has been shown to modulate calcineurin activity under physiological and pathological conditions. Unfortunately, the members of this(More)
It has long been suspected that chronic stress can exacerbate, or even cause, disease. We now propose that the RCAN1 gene, which can generate several RCAN1 protein isoforms, may be at least partially responsible for this phenomenon. We review data showing that RCAN1 proteins can be induced by multiple stresses, and present new data also implicating(More)
The proopiomelanocortin (POMC) and the corticotropin releasing hormone receptor (CRH-R) genes are expressed in the skin of the C57BL/6 mouse throughout the entire hair cycle, and CRH immunoreactivity is present in the pilosebaceous unit of the hair follicle and the epidermis. These findings suggest that some components of hypothalamo-pituitary axis are(More)