Spinal Cord

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: 
PloS One

BACKGROUND: Mutation in the ubiquitously expressed cytoplasmic superoxide dismutase (SOD1) causes an inherited form of Amyotrophic Lateral Sclerosis (ALS). Mutant synthesis in motor neurons drives disease onset and early disease progression. Previous experimental studies have shown that spinal grafting of human fetal spinal neural stem cells (hNSCs) into the lumbar spinal cord of SOD1(G93A) rats leads to a moderate therapeutical effect as evidenced by local ?-motoneuron sparing and extension of lifespan.

Author(s): 
Hefferan, Michael P.
Galik, Jan
Kakinohana, Osamu
Sekerkova, Gabriela
Santucci, Camila
Marsala, Silvia
Navarro, Roman
Hruska-Plochan, Marian
Johe, Karl
Feldman, Eva
Cleveland, Don W.
Marsala, 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
Publication Title: 
Human Molecular Genetics

In amyotrophic lateral sclerosis (ALS), the progressive loss of motor neurons is accompanied by extensive muscle denervation, resulting in paralysis and ultimately death. Upregulation of amyloid beta (A4) precursor protein (APP) in muscle fibres coincides with symptom onset in both sporadic ALS patients and the SOD1(G93A) mouse model of familial ALS.

Author(s): 
Bryson, J. Barney
Hobbs, Carl
Parsons, Michael J.
Bosch, Karen D.
Pandraud, Amelie
Walsh, Frank S.
Doherty, Patrick
Greensmith, Linda
Publication Title: 
Neuromolecular Medicine

A common cause of amyotrophic lateral sclerosis is mutations in superoxide dismutase-1, which provoke the disease by an unknown mechanism. We have previously found that soluble hydrophobic misfolded mutant human superoxide dismutase-1 species are enriched in the vulnerable spinal cords of transgenic model mice. The levels were broadly inversely correlated with life spans, suggesting involvement in the pathogenesis.

Author(s): 
Zetterstrˆm, Per
Graffmo, Karin S.
Andersen, Peter M.
Br‰nnstrˆm, Thomas
Marklund, Stefan L.
Publication Title: 
PloS One

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive paralysis due to motor neuron death. Several lines of published evidence suggested that inhibition of epidermal growth factor receptor (EGFR) signaling might protect neurons from degeneration. To test this hypothesis in vivo, we treated the SOD1 transgenic mouse model of ALS with erlotinib, an EGFR inhibitor clinically approved for oncology indications.

Author(s): 
Le Pichon, Claire E.
Dominguez, Sara L.
Solanoy, Hilda
Ngu, Hai
Lewin-Koh, Nicholas
Chen, Mark
Eastham-Anderson, Jeffrey
Watts, Ryan
Scearce-Levie, Kimberly
Publication Title: 
Autophagy

Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron disease with no current effective treatment. Accumulation of abnormal protein inclusions containing SOD1, TARDBP, FUS, among other proteins, is a pathological hallmark of ALS. Autophagy is the major degradation pathway involved in the clearance of damaged organelles and protein aggregates. Although autophagy has been shown to efficiently degrade ALS-linked mutant protein in cell culture models, several studies suggest that autophagy impairment may also contribute to disease pathogenesis.

Author(s): 
Castillo, Karen
Nassif, Melissa
Valenzuela, Vicente
Rojas, Fabiola
Matus, Soledad
Mercado, Gabriela
Court, Felipe A.
van Zundert, Brigitte
Hetz, Claudio
Publication Title: 
PloS One

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the spinal cord, brain stem, and motor cortex. Mutations in superoxide dismutase (SOD1) are associated with familial ALS and lead to SOD1 protein misfolding and aggregation. Here we show that the molecular chaperone, HSJ1 (DNAJB2), mutations in which cause distal hereditary motor neuropathy, can reduce mutant SOD1 aggregation and improve motor neuron survival in mutant SOD1 models of ALS.

Author(s): 
Novoselov, Sergey S.
Mustill, Wendy J.
Gray, Anna L.
Dick, James R.
Kanuga, Naheed
Kalmar, Bernadett
Greensmith, Linda
Cheetham, Michael E.
Publication Title: 
Brain Research

Central nervous system (CNS) development, homeostasis, stress responses, and plasticity are all mediated by epigenetic mechanisms that modulate gene expression and promote selective deployment of functional gene networks in response to complex profiles of interoceptive and environmental signals. Thus, not surprisingly, disruptions of these epigenetic processes are implicated in the pathogenesis of a spectrum of neurological and psychiatric diseases.

Author(s): 
Qureshi, Irfan A.
Mattick, John S.
Mehler, Mark F.
Publication Title: 
Psychoneuroendocrinology

For the present purpose, love is defined as one's having stimulation that one desires. The nature of the stimulation can range on a continuum from the most abstract cognitive, to the most direct sensory, forms. Thus, this definition of love encompasses having an emotional bond with a person for whom one yearns, as well as having sensory stimulation that one desires. We address some of the physiological and perceptual consequences both of having, and of not having, love.

Author(s): 
Komisaruk, B. R.
Whipple, B.

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