Disease Models, Animal

Publication Title: 
Mutation Research

During the course of normal respiration, reactive oxygen species are produced which are particularly detrimental to mitochondrial function. This is shown by recent studies with a mouse that lacks the mitochondrial form of superoxide dismutase (Sod2). Tissues that are heavily dependent on mitochondrial function such as the brain and heart are most severely affected in the Sod2 mutant mouse.

Author(s): 
Melov, S.
Coskun, P. E.
Wallace, D. C.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

In investigating the role of metal ions in the pathogenesis of Huntington's disease, we examined the effects of clioquinol, a metal-binding compound currently in clinical trials for Alzheimer's disease treatment, on mutant huntingtin-expressing cells. We found that PC12 cells expressing polyglutamine-expanded huntingtin exon 1 accumulated less mutant protein and showed decreased cell death when treated with clioquinol. This effect was polyglutamine-length-specific and did not alter mRNA levels or protein degradation rates.

Author(s): 
Nguyen, Trent
Hamby, Aaron
Massa, Stephen M.
Publication Title: 
Journal of Neurochemistry

The search for effective treatments that prevent oxidative stress associated with premature ageing and neurodegenerative diseases is an important area of neurochemical research. As age- and disease-related oxidative stress is frequently associated with mitochondrial dysfunction, amphiphilic antioxidant agents of high stability and selectivity that target these organelles can provide on-site protection.

Author(s): 
Poeggeler, Burkhard
Durand, GrÈgory
Polidori, Ange
Pappolla, Miguel A.
Vega-Naredo, Ignacio
Coto-Montes, Ana
Bˆker, Jutta
Hardeland, R¸diger
Pucci, Bernard
Publication Title: 
Journal of the Neurological Sciences

Amyotrophic lateral sclerosis (ALS) is a progressive disease which is caused by degeneration of motor neurons in the central nervous system. The incidence of ALS is higher in men than women, but the female advantage disappears with increased age. Here, we report evidence that the female advantage is due to the protective role of estrogen. In an ALS mouse model carrying the human Cu/Zn superoxide dismutase (hSOD1) G93A transgene, ovariectomy did not alter the onset age of the disease while reducing the female lifespan by 7 days and making it comparable to that of the male transgenic mice.

Author(s): 
Choi, Chan-Il
Lee, Young-Don
Gwag, Byoung Joo
Cho, Sung Ig
Kim, Sung-Soo
Suh-Kim, Haeyoung
Publication Title: 
Human Molecular Genetics

Autophagy is a highly regulated intracellular process involved in the turnover of most cellular constituents and in the maintenance of cellular homeostasis. It is well-established that the basal autophagic activity of living cells decreases with age, thus contributing to the accumulation of damaged macromolecules during aging. Conversely, the activity of this catabolic pathway is required for lifespan extension in animal models such as Caenorhabditis elegans and Drosophila melanogaster.

Author(s): 
MariÒo, Guillermo
Ugalde, Alejandro P.
Salvador-Montoliu, Natalia
Varela, Ignacio
QuirÛs, Pedro M.
CadiÒanos, Juan
van der Pluijm, Ingrid
Freije, JosÈ M. P.
LÛpez-OtÌn, Carlos
Publication Title: 
Human Molecular Genetics

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is caused by loss of functional survival motor neuron 1 (SMN1), resulting in death of spinal motor neurons. Current therapeutic research focuses on modulating the expression of a partially functioning copy gene, SMN2, which is retained in SMA patients. However, a treatment strategy that improves the SMA phenotype by slowing or reversing the skeletal muscle atrophy may also be beneficial. Myostatin, a member of the TGF-beta super-family, is a potent negative regulator of skeletal muscle mass.

Author(s): 
Rose, Ferrill F.
Mattis, Virginia B.
Rindt, Hansjˆrg
Lorson, Christian L.
Publication Title: 
Experimental & Molecular Medicine

Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1(G93A)) transgenic mice.

Author(s): 
Park, Sungju
Kim, Hyoung-Tae
Yun, Seokkwan
Kim, Il-Sun
Lee, Jiyoon
Lee, Il-Shin
Park, Kook In
Publication Title: 
NestlÈ Nutrition Workshop Series. Paediatric Programme

The focus here is on research involving long-term calorie restriction (CR) to prevent or delay the incidence of the metabolic syndrome with age. The current societal environment is marked by overabundant accessibility of food coupled with a strong trend to reduced physical activity, both leading to the development of a constellation of disorders including central obesity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome). Prolonged CR has been shown to extend median and maximal lifespan in a variety of lower species (yeast, worms, fish, rats, and mice).

Author(s): 
Ravussin, Eric
Redman, Leanne M.
Publication Title: 
Cellular and Molecular Neurobiology

The nicotinamide adenine dinucleotide (NAD)-activated protein deacetylase Sir2p/Sirt1 has been strongly implicated in the modulation of replicative lifespan and promotion of longevity. Part of Sirt1's capacity for lifespan extension in complex organisms may be attributed to its protective activity against neuronal degeneration. Manipulation of Sirt1's activity or levels by pharmacological and genetic means in several models of neurodegenerative diseases demonstrated its neuroprotective credentials.

Author(s): 
Tang, Bor Luen
Publication Title: 
Cancer Research

C57BL/6J mice carrying the Min allele of Adenomatous polyposis coli (Apc) develop numerous adenomas along the entire length of the intestine and consequently die at an early age. This short lifespan would prevent the accumulation of somatic genetic mutations or epigenetic alterations necessary for tumor progression. To overcome this limitation, we generated F(1) Apc(Min/+) hybrids by crossing C57BR/cdcJ and SWR/J females to C57BL/6J Apc(Min/+) males. These hybrids developed few intestinal tumors and often lived longer than 1 year.

Author(s): 
Halberg, Richard B.
Waggoner, Jesse
Rasmussen, Kristen
White, Alanna
Clipson, Linda
Prunuske, Amy J.
Bacher, Jeffery W.
Sullivan, Ruth
Washington, Mary Kay
Pitot, Henry C.
Petrini, John H. J.
Albertson, Donna G.
Dove, William F.

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