Tools and reagents are
freely available at www.optogenetics.org and www.addgene.org, and hands-on optogenetics training courses are available (www.optogenetics.org). We gratefully acknowledge that this research direction was launched with funding beginning July 2004 to K.D. as principal investigator from the National Institutes of Health, from the Stanford Department of Psychiatry, and from the Stanford Department of Bioengineering (www.optogenetics.org/funding). Both this initial microbial opsin work and all subsequent work at Stanford over the years have been financially supported with grants awarded to K.D. from many generous agencies and donors, including from the National Institute of Mental Health, the NIH Director’s Pioneer Award, the National Institute on Smad inhibitor Drug Abuse, the National Institute of Neurological Disorders and Stroke, the National Science Foundation, the Michael J Fox Foundation, the Defense Advanced Research
Projects Agency, the California Institute of Regenerative Medicine, and the Coulter, Culpeper, Klingenstein, Whitehall, McKnight, Yu, Woo, Snyder, and Keck Foundations. We thank the many supportive laboratories and members of the Stanford community for collaboration, advice, and equipment-sharing over this time, as well as the many members of the K.D. laboratory in the Clark Center at Stanford over the years. O.Y. is supported by the International Human Frontier Science Program. L.E.F is supported by the Stanford MSTP program, T.J.D. is supported by the Berry Postdoctoral Fellowship, isothipendyl and M.M. is supported Nintedanib by Bio-X, Siebel, and SGF fellowships. “
“Neurodegenerative
diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotropic lateral sclerosis (ALS) each primarily affect defined subsets of neurons and involve characteristic ranges of pathological and molecular features. The main risk factor for NDDs is advancing age. The accumulation of distinct protein-based macroscopic deposits is a hallmark of NDDs. Although phenotypic variations and comorbidities are frequent, the composition and distribution of the deposits is a defining property of each NDD, and some of the mutations associated with familial cases of the diseases affect folding of the major protein components of the deposits. Accordingly, NDDs are currently viewed as cerebral proteopathies, in which the accumulation of particular misfolded proteins is a key causative factor (e.g., Haass and Selkoe, 2007, Golde and Miller, 2009 and Frost and Diamond, 2010). Since the misfolding proteins implicated in the etiology of NDDs are expressed ubiquitously, a major unresolved question is how deposit formation and pathology nevertheless selectively target specific subpopulations of neurons.