DEVELOPMENT OF D-PINITOL IN THE TREATMENT OF ALZHEIMER'S DISEASE

D-松醇在阿尔茨海默病治疗中的开发

• 批准号: 7953697
• 负责人: HILLEL GROSSMAN
• 金额: $ 1.74万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953697
• 关键词: Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Automobile Driving; Brain; Cerebrum; Clinical; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Deposition; Development; Disease; Dose; Elderly; Epidemiologic Studies; Fasting; Food Supplements; Funding; Generations; Grant; Human; Impaired cognition; Inflammation; Institution; Insulin; Insulin Resistance; Mediating; Memory impairment; Morbidity - disease rate; Neurofibrillary Tangles; Non-Insulin-Dependent Diabetes Mellitus; Pathology; Patients; Peptides; Phosphatidylinositol Phosphates; Plasma; Research; Research Personnel; Resources; Risk; Source; United States National Institutes of Health; Work; abeta accumulation; glucose transport; insulin sensitivity; insulin sensitizing drugs; mortality; neuropathology; pinitol; preclinical study; response; secretase

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer's disease (AD), a leading cause of morbidity and mortality in older adults, is characterized by cognitive impairment and neuropathological features, including beta amyloid (A ) deposition, neurofibrillary tangles, and increased cerebral inflammation. Convergent evidence has revealed an association between AD and insulin resistance. A substantial number of patients with AD demonstrate elevated fasting plasma insulin and reduced insulin sensitivity. These findings are supported by epidemiological studies that demonstrate an association between non-insulin dependent type-2 diabetes (NIDDM), a condition often associated with insulin resistance, and increased risk for memory impairment and AD (Kuisisto et al., 1997; Ott et al., 1999). We hypothesized that when treated early, insulin resistance and associated brain responses in AD may be reversible with tolerable doses of insulin sensitizer agents and that this treatment may also arrest, and potentially reverse, the clinical and neuropathological progression of AD type cognitive impairment. D-pinitol, an approved food supplement has been shown to have insulin-sensitizing effects in human studies. Moreover, in preclinical studies it interferes with the accumulation of beta amyloid, an important step in the development of Alzheimer's pathology. Hypothesis: The working hypothesis driving this application is that the insulin sensitizer agent d-pinitol, structurally related to the phosphatidylinositol phosphates that participate in insulin-mediated stimulation of glucose transport may beneficially influence AD-type amyloid neuropathology through inhibition of ?-secretase activity in the brain resulting in reduced generation of amyloidogenic A?1-42 and A?1-40 peptides

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 阿尔茨海默氏病（AD）是老年人发病率和死亡率的主要原因，其特征是认知障碍和神经病理学特征，包括β-淀粉样蛋白（A）沉积，神经纤维缠结缠结和脑炎增加。收敛证据揭示了AD和胰岛素抵抗之间的关联。大量AD患者表现出升高的空腹血浆胰岛素和胰岛素敏感性降低。这些发现得到了流行病学研究的支持，这些研究表明非胰岛素依赖性2型糖尿病（NIDDM）之间存在关联，这种疾病通常与胰岛素抵抗有关，并增加了记忆障碍和AD的风险（Kuisisto等，1997; Ott等，1999）。我们假设，在早期治疗时，AD中的胰岛素抵抗和相关的大脑反应可能会因胰岛素敏化剂的可耐受剂量而可逆，并且这种治疗方法也可能会阻止，并且可能会逆转AD类型认知障碍的临床和神经病理学进展。 D-Pinitol（已批准的食物补充剂）在人类研究中具有胰岛素敏感性的作用。此外，在临床前研究中，它会干扰β-淀粉样蛋白的积累，这是阿尔茨海默病理发展的重要一步。 假设： 驱动该应用的工作假设是，与参与胰岛素介导的葡萄糖转运刺激的胰岛素敏化剂D-与磷脂酰肌醇磷酸盐的结构相关，可能会通过抑制4粒脑酶促进糖化酶的活性而有益地影响AD型淀粉样神经病理学，并抑制氧化酶的活性。 A？1-40肽