Core A will be responsible for the general organization of the program and for promoting productive interactions among all projects and cores and between this program and the scientific community. The core will also promote, monitor, and report on the progress of the program. To achieve these goals, we propose the following specific aims.
Aim 1 : Define the overall organization of the program and adjust its structure according to research developments and opportunities. The core leader has developed an interactive program in disease-related neuroscience at the applicant institution, and the current proposal emerged directly from these research activities. The proposal also relates closely to the core leader's long-standing and fruitful collaboration with Dr. Masliah at UCSD, whose interests overlap widely with those of the other members of this program.
Aim 2 : Promote exchange among the projects and cores and monitor their progress toward the goals of the program. Research in this program will be carried out in five projects and four cores. Core A will organize regular meetings of all program personnel to review and discuss progress and adjust experimental strategies as needed. We will continue to encourage and facilitate the development of web pages and databases to promote the exchange of information among program members.
Aim 3 : Ensure the efficient generation and safe storage of data, the timely preparation of progress reports, and the dissemination of research findings and materials. This will include instruction in safety procedures, backup of electronic files, and assistance with manuscript preparation, travel arrangements, and shipments of materials.
Aim 4 : Arrange for external reviews of the research activities in the projects and cores and foster the acquisition of new approaches that could promote the progress of the program as a whole. The entire program will be reviewed annually by members of an external advisory board. Additional experts will be invited to provide ad hoc input on specific components.
Aim 5 : Play an active role in the further development of UCSF's Mission Bay campus and help the project/core leaders take advantage of the many conceptual and technological advances that will emerge at this site. During the preceding funding period, we relocated all three Gladstone Institutes, and with them most of this program, to the Mission Bay campus. By consolidating our laboratories, cores, and animal care facilities into the same research building located within walking distance from many UCSF colleagues with overlapping interests, this move further enhanced the strength and potential of our program. Our new environment will greatly contribute to the success of the research proposed in this renewal application.

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National Institute on Aging (NIA)
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J. David Gladstone Institutes
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Valera, Elvira; Spencer, Brian; Mott, Jennifer et al. (2017) MicroRNA-101 Modulates Autophagy and Oligodendroglial Alpha-Synuclein Accumulation in Multiple System Atrophy. Front Mol Neurosci 10:329
Valera, Elvira; Spencer, Brian; Fields, Jerel A et al. (2017) Combination of alpha-synuclein immunotherapy with anti-inflammatory treatment in a transgenic mouse model of multiple system atrophy. Acta Neuropathol Commun 5:2
Overk, Cassia; Masliah, Eliezer (2017) Perspective on the calcium dyshomeostasis hypothesis in the pathogenesis of selective neuronal degeneration in animal models of Alzheimer's disease. Alzheimers Dement 13:183-185
Spencer, Brian; Desplats, Paula A; Overk, Cassia R et al. (2016) Reducing Endogenous ?-Synuclein Mitigates the Degeneration of Selective Neuronal Populations in an Alzheimer's Disease Transgenic Mouse Model. J Neurosci 36:7971-84
Spencer, Brian; Kim, Changyoun; Gonzalez, Tania et al. (2016) ?-Synuclein interferes with the ESCRT-III complex contributing to the pathogenesis of Lewy body disease. Hum Mol Genet 25:1100-15
Valera, Elvira; Masliah, Eliezer (2016) Therapeutic approaches in Parkinson's disease and related disorders. J Neurochem 139 Suppl 1:346-352
Spencer, Brian; Potkar, Rewati; Metcalf, Jeff et al. (2016) Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease. J Biol Chem 291:1905-20
Valera, E; Monzio Compagnoni, G; Masliah, E (2016) Review: Novel treatment strategies targeting alpha-synuclein in multiple system atrophy as a model of synucleinopathy. Neuropathol Appl Neurobiol 42:95-106
Valera, Elvira; Spencer, Brian; Masliah, Eliezer (2016) Immunotherapeutic Approaches Targeting Amyloid-?, ?-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders. Neurotherapeutics 13:179-89
Valera, Elvira; Masliah, Eliezer (2016) Combination therapies: The next logical Step for the treatment of synucleinopathies? Mov Disord 31:225-34

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