Brain

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: 
Journal of Cell Science

In mammalian cells, products of the INK4a-ARF locus play major roles in senescence and tumour suppression in different contexts, whereas the adjacent INK4b gene is more generally associated with transforming growth factor beta (TGF-beta)-mediated growth arrest. As the chicken genome does not encode an equivalent of INK4a, we asked whether INK4b and/or ARF contribute to replicative senescence in chicken cells.

Author(s): 
Kim, Soo-Hyun
Rowe, Janice
Fujii, Hideta
Jones, Rebecca
Schmierer, Bernhard
Kong, Byung-Whi
Kuchler, Karl
Foster, Douglas
Ish-Horowicz, David
Peters, Gordon
Publication Title: 
Aging Cell

Brain aging is associated with a progressive imbalance between antioxidant defenses and intracellular concentrations of reactive oxygen species (ROS) as exemplified by increases in products of lipid peroxidation, protein oxidation, and DNA oxidation. Oxidative conditions cause not only structural damage but also changes in the set points of redox-sensitive signaling processes including the insulin receptor signaling pathway. In the absence of insulin, the otherwise low insulin receptor signaling is strongly enhanced by oxidative conditions.

Author(s): 
Drˆge, Wulf
Schipper, Hyman M.
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: 
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: 
CNS neuroscience & therapeutics

Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of adults which preferentially attacks the neuromotor system. Riluzole has been used as the only approved treatment for amyotrophic lateral sclerosis since 1995, but its mechanism(s) of action in slowing the progression of this disease remain obscure. Searching PubMed for "riluzole" found 705 articles published between January 1996 and June 2009.

Author(s): 
Bellingham, Mark C.
Publication Title: 
Experimental Gerontology

Signaling by target of rapamycin (mTOR in mammals) has been shown to modulate lifespan in several model organisms ranging from yeast to mice. In mice, reduced mTOR signaling by chronic rapamycin treatment leads to life span extension, raising the possibility that rapamycin and its analogs may benefit the aging brain and serve as effective treatments of age-related neurodegenerative diseases. Here, we review mTOR signaling and how neurons utilize mTOR to regulate brain function, including regulation of feeding, synaptic plasticity and memory formation.

Author(s): 
Garelick, Michael G.
Kennedy, Brian K.
Publication Title: 
Consciousness and Cognition

The continual background awareness of duration is an essential structure of consciousness, conferring temporal extension to the many objects of awareness within the evanescent sensory present. Seeking the possible neural correlates of ubiquitous temporal awareness, this article reexamines fMRI data from off-task "default mode" (DM) periods in 25 healthy subjects studied by Grady et al. ("Age-related Changes in Brain Activity across the Adult Lifespan,"Journal of Cognitive Neuroscience 18(2), 2005).

Author(s): 
Lloyd, Dan
Publication Title: 
NestlÈ Nutrition Workshop Series. Paediatric Programme

Insulin and insulin-like signaling regulate survival and lifespan in a variety of animal species, from nematodes and flies to higher vertebrates and mammals. Recently, it was shown that brain IGF-I receptor and brain IRS2 control mammalian lifespan, and that this occurs through neuroendocrine mechanisms, control of energy metabolism and modified stress resistance. Furthermore, it was demonstrated that insulin receptor substrate molecules are implicated downstream of insulin and IGF receptors in the extension of lifespan.

Author(s): 
Holzenberger, Martin
Publication Title: 
European journal of human genetics: EJHG

Spinal muscular atrophy (SMA) is the leading genetic cause of early childhood death worldwide and no therapy is available today. Many drugs, especially histone deacetylase inhibitors (HDACi), increase SMN levels. As all HDACi tested so far only mildly ameliorate the SMA phenotype or are unsuitable for use in humans, there is still need to identify more potent drugs. Here, we assessed the therapeutic power of the pan-HDACi JNJ-26481585 for SMA, which is currently used in various clinical cancer trials.

Author(s): 
Schreml, Julia
Riessland, Markus
Paterno, Mario
Garbes, Lutz
Roflbach, Kristina
Ackermann, Bastian
Kr‰mer, Jan
Somers, Eilidh
Parson, Simon H.
Heller, Raoul
Berkessel, Albrecht
Sterner-Kock, Anja
Wirth, Brunhilde

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