Neural Cell News Volume 6.48 | Dec 5 2012

β-Arrestin 2 Regulates Aβ Generation and γ-Secretase Activity in Alzheimer’s Disease
Researchers report that β-arrestin 2 expression is elevated in two independent cohorts of individuals with Alzheimer’s disease. Overexpression of β-arrestin 2 leads to an increase in amyloid-β (Aβ) peptide generation, whereas genetic silencing of Arrb2 (encoding β-arrestin 2) reduces generation of Aβ in cell cultures and in Arrb2^−/− mice. [Nat Med] Abstract | Press Release

Autologous Mesenchymal Stem Cell-Derived Dopaminergic Neurons Function in Parkinsonian Macaques
The authors showed that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. [J Clin Invest] Full Article

Inhibition of GSK3β-Mediated BACE1 Expression Reduces Alzheimer-Associated Phenotypes
Investigators report that specific inhibition of glycogen synthase kinase 3 (GSK3)β, but not GSK3α, reduced β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1)-mediated cleavage of APP and Aβ production by decreasing BACE1 gene transcription and expression. [J Clin Invest]
Full Article | Press Release

The CB₁ Cannabinoid Receptor Drives Corticospinal Motor Neuron Differentiation through the Ctip2/Satb2 Transcriptional Regulation Axis
Scientists showed that the CB₁ receptor, by preventing Satb2 (special AT-rich binding protein 2)-mediated repression, increased Ctip2 (COUP-TF interacting protein 2) promoter activity, and Ctip2-positive neuron generation. [J Neurosci] Abstract

Chemotactic Recruitment of Adult Neural Progenitor Cells into Multifunctional Hydrogels Providing Sustained SDF-1α Release and Compatible Structural Support
Without chemotactic cues and structural support, cavitary brain lesions typically fail to recruit endogenous neural progenitor cells. Toward resolving this, the authors engineered multifunctional biomaterials comprising injectable gelatin-hydroxyphenylpropionic acid hydrogels and dextran sulfate/chitosan polyelectrolyte complex nanoparticles that delivered stromal cell-derived factor-1α (SDF-1α). [FASEB J] Abstract

Experimental and Clinical Factors Influencing Long-Term Stable In Vitro Expansion of Multipotent Neural Cells from Human Adult Temporal Lobes
Autologous adult human neural stem cells may be used for regenerative cell therapies to bypass potential ethical problems. However, stable in vitro expansion protocols and experimental/clinical factors influencing primary cultures need to be further elucidated for clinically applicable techniques. To address these issues, scientists obtained biopsy specimens from 23 temporal lobe epilepsy patients and adult human multipotent neural cells were primarily cultured in a defined attachment culture condition. [Exp Neurol] Abstract

GH Mediates Exercise-Dependent Activation of SVZ Neural Precursor Cells in Aged Mice
The authors demonstrated, both in vivo and in vitro, that growth hormone (GH) mediates precursor cell activation in the subventricular zone (SVZ) of the aged brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. [PLoS One] Full Article

Duration of Shh Signaling Contributes to mDA Neuron Diversity
Investigators demonstrated that the loss of sonic hedgehog (Shh) signaling in Shh expressing cells results in a transient increase in proliferation and subsequent depletion of midbrain dopamine (mDA) neuron progenitors in the posterior ventral mesencephalon due to the facilitated cell cycle exit. [Dev Biol] Abstract

Upregulation of Mesencephalic Astrocyte-Derived Neurotrophic Factor in Glial Cells Is Associated with Ischemia-Induced Glial Activation
Researchers found that mesencephalic astrocyte-derived neurotrophic factor (MANF) was predominantly expressed in neurons in both normal and ischemic cortex. MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. [J Neuroinflamm]
Abstract | Full Article | Press Release

Merck Initiates Phase II/III Study of Investigational BACE Inhibitor, MK-8931, for Treatment of Alzheimer’s Disease
Merck announced it has started a phase II/III clinical trial designed to evaluate the safety and efficacy of MK-8931 versus placebo in patients with mild-to-moderate Alzheimer’s disease. [Merck & Co., Inc.] Press Release

Fisher Center for Alzheimer’s Research Foundation Receives Coveted Four-Star Rating from Charity Navigator for the Seventh Time
The Fisher Center for Alzheimer’s Research Foundation announced it has received the highest, four-star, rating for the second consecutive year from Charity Navigator’s. Only 17% of the charities rated by Charity Navigator have received two or more consecutive four-star evaluations, indicating that Fisher Center for Alzheimer’s Research Foundation outperforms most other charities in America. [The Fisher Center for Alzheimer’s Research Foundation] Press Release

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