Huntington's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Huntington's Disease, including details on genetics, causes, symptoms, treatment.

Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseases.

Yang L, Calingasan NY, Wille EJ, Cormier K, Smith K, Ferrante RJ, Beal MF

Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York 10021, USA.

Coenzyme Q(10) (CoQ(10)) and creatine are promising agents for neuroprotection in neurodegenerative diseases via their effects on improving mitochondrial function and cellular bioenergetics and their properties as antioxidants. We examined whether a combination of CoQ(10) with creatine can exert additive neuroprotective effects in a MPTP mouse model of Parkinson's disease, a 3-NP rat model of Huntington's disease (HD) and the R6/2 transgenic mouse model of HD. The combination of the two agents produced additive neuroprotective effects against dopamine depletion in the striatum and loss of tyrosine hydroxylase neurons in the substantia nigra pars compacta (SNpc) following chronic subcutaneous administration of MPTP. The combination treatment resulted in significant reduction in lipid peroxidation and pathologic alpha-synuclein accumulation in the SNpc neurons of the MPTP-treated mice. We also observed additive neuroprotective effects in reducing striatal lesion volumes produced by chronic subcutaneous administration of 3-NP to rats. The combination treatment showed significant effects on blocking 3-NP-induced impairment of glutathione homeostasis and reducing lipid peroxidation and DNA oxidative damage in the striatum. Lastly, the combination of CoQ(10) and creatine produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice. These findings suggest that combination therapy using CoQ(10) and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson's disease and HD.

Published 29 May 2009 in J Neurochem, 109(5): 1427-39.
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Articles on Huntington's Disease published 11 May 2009:

Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs.   Nat Biotechnol, 27(5): 478-84.

Expanded trinucleotide repeats cause many neurological diseases. These include Machado-Joseph disease (MJD) and Huntington's disease (HD), which are caused by expanded CAG repeats within an allele of the ataxin-3 (ATXN3) and huntingtin (HTT) genes, respectively. Silencing expression of these genes is a promising therapeutic strategy, but indiscriminate inhibition of both the mutant and wild-type alleles may lead to toxicity, and allele-specific approaches have required polymorphisms that differ ... [Abstract] [Full-text]

Articles on Huntington's Disease published 27 April 2009:

Regulator of calcineurin (RCAN1-1L) is deficient in Huntington disease and protective against mutant huntingtin toxicity in vitro.   J Biol Chem, 284(18): 11845-53.

Our work suggests an important new link between the RCAN1 gene and Huntington disease. Huntington disease is caused by expansion of glutamine repeats in the huntingtin protein. How the huntingtin protein with expanded polyglutamines (mutant huntingtin) causes the disease is still unclear, but phosphorylation of huntingtin appears to be protective. Increased huntingtin phosphorylation can be produced either by inhibition of the phosphatase calcineurin or by activation of the Akt kinase. The ... [Abstract] [Full-text]

Articles on Huntington's Disease published 23 April 2009:

Cross-seeding fibrillation of Q/N-rich proteins offers new pathomechanism of polyglutamine diseases.   J Neurosci, 29(16): 5153-62.

A pathological hallmark of the Huntington's disease (HD) is intracellular inclusions containing a huntingtin (Htt) protein with an elongated polyglutamine tract. Aggregation of mutant Htt causes abnormal protein-protein interactions, and the functional dysregulation of aggregate-interacting proteins (AIPs) has been proposed as a pathomechanism of HD. Despite this, a molecular mechanism remains unknown how Htt aggregates sequester AIPs. We note an RNA-binding protein, TIA-1, as a model of AIPs ... [Abstract] [Full-text]

Articles on Huntington's Disease published 25 March 2009:

Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington's disease knockin mice.   Proc Natl Acad Sci U S A, 106(12): 4906-11.

Cognitive problems occur in asymptomatic gene carriers of Huntington's disease (HD), and mouse models of the disease exhibit impaired learning and substantial deficits in the cytoskeletal changes that stabilize long-term potentiation (LTP). The latter effects may be related to the decreased production of brain-derived neurotrophic factor (BDNF) associated with the HD mutation. This study asked whether up-regulating endogenous BDNF levels with an ampakine, a positive modulator of AMPA-type ... [Abstract] [Full-text]

Articles on Huntington's Disease published 23 March 2009:

Glutamate toxicity in the striatum of the R6/2 Huntington's disease transgenic mice is age-dependent and correlates with decreased levels of glutamate transporters.   Neurobiol Dis, 34(1): 78-86.

Glutamate excitotoxicity has been implicated in the neuropathology of Huntington's disease (HD), due to the toxicity of glutamate receptor agonists on striatal medium spiny neurons (MSN), the most affected neuronal population in HD. Previous studies showed functional alterations of NMDA glutamate receptors and decreased expression of glutamate transporters in transgenic models and HD patients, suggesting the presence of excitotoxic damage. We have studied the vulnerability of the striatum to ... [Abstract] [Full-text]

Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease.   Neurobiol Dis, 34(1): 40-50.

Members of the GDNF family of ligands, including neurturin (NTN), have been implicated as potential therapeutic agents for Huntington's disease (HD). The present study examined the ability of CERE-120 (AAV2-NTN) to provide structural and functional protection in the N171-82Q transgenic HD mouse model. AAV2-NTN therapy attenuated rotorod deficits in this mutant relative to control treated transgenics (p<0.01). AAV2-NTN treatment significantly reduced the number of transgenic mice that ... [Abstract] [Full-text]

Articles on Huntington's Disease published 20 March 2009:

Functional imaging in Huntington's disease.   Exp Neurol, 216(2): 272-7.

Huntington's disease (HD) is a genetic brain disease characterized by loss of capacity in movement control, cognition, and emotional regulation over a period of about 30 years. Since it is well established that clinical impairments and brain atrophy can be detected decades prior to receiving a clinical diagnosis, functional neuroimaging efforts have gained momentum in HD research. In most brain disorders, there is accumulating evidence that the clinical manifestations of disease do not simply ... [Abstract] [Full-text]

Plasma homovanillic acid and prolactin in Huntington's disease.   Neurochem Res, 34(5): 917-22.

Dopaminergic activity is expected to be altered in patients with Huntington's disease (HD) and be related to factors like duration and severity of illness or patients' specific symptomatology like dementia, depression, or psychotic features. We assessed plasma homovanillic acid (pHVA) and plasma prolactin (pPRL), two correlates of dopaminergic activity, in 116 subjects with CAG repeats expansion in the HD gene, 26 presymptomatic (18 females) and 90 with overt symptomatology (43 females). ... [Abstract] [Full-text]

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