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The incidence of amyloid plaques, composed mainly of bamyloid peptides (Ab), does not correlate well with the severity of neurodegeneration in patients with Alzheimer's disease (AD). The effects of Ab 42 on neurons or neural stem cells (NSCs) in terms of the aggregated form remain controversial. We prepared three forms of oligomeric, fibrillar, and monomeric Ab 42 peptides and investigated their effects on the proliferation and neural differentiation of adult NSCs, according to the degree of aggregation or concentration. A low micromolar concentration (1 lmol/L) of oligomeric Ab 42 increased the proliferation of adult NSCs remarkably in a neurosphere assay. It also enhanced the neuronal differentiation of adult NSCs and their ability to migrate. These results provide us with valuable information regarding the effects of Ab 42 on NSCs in the brains of patients with AD.

The treatment of Parkinson's disease (PD) using stem cells has long been the focus of many researchers, but the ideal therapeutic strategy has not yet been developed. The consistency and high reliability of the experimental results confirmed by animal models are considered to be a critical factor in the stability of stem cell transplantation for PD. Therefore, the aim of this study was to investigate the preventive and therapeutic potential of human adipose-derived stem cells (hASC) for PD and was to identify the related factors to this therapeutic effect. The hASC were intravenously injected into the tail vein of a PD mouse model induced by 6-hydroxydopamine. Consequently, the behavioral performances were significantly improved at 3 weeks after the injection of hASC. Additionally, dopaminergic neurons were rescued, the number of structure-modified mitochondria was decreased, and mitochondrial complex I activity was restored in the brains of the hASC-injected PD mouse model. Overall, this study underscores that intravenously transplanted hASC may have therapeutic potential for PD by recovering mitochondrial functions.

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Parkinson's disease (PD) is a common neurodegenerative disorder and is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although many studies showed that the aggregation of alpha-synuclein might be involved in the pathogenesis of PD, its protective properties against oxidative stress remain to be elucidated. In this study, human wild type and mutant alpha-synuclein genes were fused with a gene fragment encoding the nine amino acid transactivator of transcription (Tat) protein transduction domain of HIV-1 in a bacterial expression vector to produce a genetic in-frame WT Tat-alpha-synuclein (wild type) and mutant Tat-alpha-synucleins (mutants; A30P and A53T), respectively, and we investigated the protective effects of wild type and mutant Tat-alpha-synucleins in vitro and in vivo. WT Tat-alpha-synuclein rapidly transduced into an astrocyte cells and protected the cells against paraquat induced cell death. However, mutant Tat-alpha-synucleins did not protect at all. In the mice models exposed to the herbicide paraquat, the WT Tat-alpha-synuclein completely protected against dopaminergic neuronal cell death, whereas mutants failed in protecting against oxidative stress. We found that these protective effects were characterized by increasing the expression level of heat shock protein 70 (HSP70) in the neuronal cells and this expression level was dependent on the concentration of transduced WT Tat-alpha-synuclein. These results suggest that transduced Tat-alpha-synuclein might protect cell death from oxidative stress by increasing the expression level of HSP70 in vitro and in vivo and this may be of potential therapeutic benefit in the pathogenesis of PD.

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Incubation of an NAD + -dependent succinic semialdehyde dehydrogenase from bovine brain with 4-dimethylaminoazobenzene-4-iodoacetamide (DABIA) resulted in a timedependent loss of enzymatic activity. This inactivation followed pseudo first-order kinetics with a second-order rate constant of 168 M. The spectrum of DABIA-labeled enzyme showed a characteristic peak of the DABIA alkylated sulfhydryl group chromophore at 436 nm, which was absent from the spectrum of the native enzyme. A linear relationship was observed between DABIA binding and the loss of enzyme activity, which extrapolates to a stoichiometry of 8.0 mol DABIA derivatives per mol enzyme tetramer. This inactivation was prevented by preincubating the enzyme with substrate, succinic semialdehyde, but not by preincubating with coenzyme NAD + . After tryptic digestion of the enzyme modified with DABIA, two peptides absorbing at 436 nm were isolated by reverse-phase HPLC. The amino acid sequences of the DABIA-labeled peptides were VCSNQFLVQR and EVGEAICTDPLVSK, respectively. These sites are identical to the putative active site sequences of other brain succinic semialdehyde dehydrogenases. These results suggest that the catalytic function of succinic semialdehyde dehydrogenase is inhibited by the specific binding of DABIA to a cysteine residue at or near its active site.Keywords: brain succinic semialdehyde dehydrogenase; DABIA; GABA shunt; reactive cysteine residues.c-Aminobutyric acid (GABA) is produced from glutamate in a reaction catalyzed by glutamate decarboxylase (GAD) and further metabolized to succinate by the successive action of GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). The carbon skeletal of GABA therefore enters the tricarboxylic acid in the form of succinate. GABA metabolism has been well characterized in the mammalian central nervous system where GABA functions as a major inhibitory neurotransmitter.SSADH, the final enzyme in GABA metabolism, has been purified from rat, human and bovine brain [1][2][3]. This enzyme is also the site of an inborn error of human metabolism [4]. In autosomal recessively inherited SSADH deficiency, now identified in more than 45 patients who manifest varying degrees of psychomotor retardation with speech delay, the normal oxidative pathway is blocked, thereby resulting in the accumulation of succinic semialdehyde (SSA). Metabolic patterns in physiologic fluids derived from patients show large increases in gamma-hydroxybutyrate (GHB) [5], the reduction product of SSA by succinic semialdehyde reductase [6]. GHB, the biochemical hallmark of SSADH deficiency, produces central nervous system effects including altered motor activity and behavior disturbances when administered to animals and humans at pharmacologic levels [7].Recently, an SSADH cDNA was cloned from rat brain and human liver [8]. The mammalian SSADH bears significant homology to bacterial NADP + -SSADH and conserved regions of aldehyde dehydrogenases, suggesting that it is a member of the aldehyde dehydrogenase superfamil...