Neurobiology of aging
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Methylene blue (MB), the first synthetic drug, has a 120-year-long history of diverse applications, both in medical treatments and as a staining reagent. In recent years there was a surge of interest in MB as an antimalarial agent and as a potential treatment of neurodegenerative disorders such as Alzheimer's disease (AD), possibly through its inhibition of the aggregation of tau protein. Here we review the history and medical applications of MB, with emphasis on recent developments.
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Neurobiology of aging · Dec 2011
ReviewFluorodeoxyglucose positron emission tomography: emerging roles in the evaluation of putative Alzheimer's disease-modifying treatments.
Alzheimer's disease (AD) is associated with characteristic and progressive reductions in flourodeoxyglucose positron emission tomography (FDG PET) measurements of the regional cerebral metabolic rate for glucose. These reductions begin years before the onset of symptoms, are correlated with clinical severity, and may help predict an affected patient's clinical course and neuropathological diagnosis. ⋯ This article considers FDG PET's role in the detection and tracking of AD, its emerging roles in the evaluation of disease-slowing treatments, some of the issues involved in the acquisition, analysis, and interpretation of FDG PET data, and the evidence needed to help qualify FDG PET and other biomarkers for use in the accelerated approval of AD-slowing treatments. It recommends scientific strategies and public policies to further establish the role of FDG PET and other AD biomarkers in therapeutic trials and find demonstrably effective disease-modifying and presymptomatic AD treatments as quickly as possible.
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Neurobiology of aging · Oct 2011
Screening for OPTN mutations in amyotrophic lateral sclerosis in a mainly Caucasian population.
Mutations in the optineurin (OPTN) gene cause amyotrophic lateral sclerosis (ALS). We previously reported 3 types of OPTN mutation in Japanese ALS subjects. ⋯ However, we could not find the meaningful OPTN mutations. The results indicate that OPTN mutations causing ALS are rare, especially in mainly Caucasian ALS subjects.
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Neurobiology of aging · Aug 2011
Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide.
Pharmacological enhancement of hippocampal neurogenesis is a therapeutic approach for improvement of cognition in learning and memory disorders such as Alzheimer's disease. Here we report the development of an 11-mer peptide that we designed based on a biologically active region of the ciliary neurotrophic factor. This peptide, Peptide 6, induced proliferation and increased survival and maturation of neural progenitor cells into neurons in the dentate gyrus of normal adult C57BL6 mice. ⋯ Thirty-day treatment of the mice with a slow release bolus of the peptide implanted subcutaneously improved reference memory of the mice in Morris water maze. Peptide 6 has a plasma half life of over 6 h, is blood-brain barrier permeable, and acts by competitively inhibiting the leukemia inhibitory factor signaling. The fact that Peptide 6 is both neurogenic and neurotrophic and that this peptide is effective when given peripherally, demonstrates its potential for prevention and treatment of learning and memory disorders.