Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution by Hemberg, Martin, De Jager, Philip L., Ransohoff, Richard M., Mathys, Hansruedi, Adaikkan, Chinnakkaruppan, Gao, Fan, Young, Jennie Zin-Ney, Manet, Elodie, Regev, Aviv, Tsai, Li-Huei

“…Here, using single-cell RNA sequencing, we determined the transcriptome of more than 1,600 individual microglia cells isolated from the hippocampus of a mouse model of severe neurodegeneration with AD-like phenotypes and of control mice at multiple time points during progression of neurodegeneration. …”
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Modelling Neurodegeneration in Saccharomyces Cerevisiae: Why Cook with Baker's Yeast? by Khurana, Vikram, Lindquist, Susan

“…Here, we describe why the budding yeast Saccharomyces cerevisiae has a unique role in the neurodegeneration armamentarium. As the best-understood and most readily analysed eukaryotic organism, S. cerevisiae is delivering mechanistic insights into cell-autonomous mechanisms of neurodegeneration at an interactome-wide scale.…”
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Human C9ORF72 Hexanucleotide Expansion Reproduces RNA Foci and Dipeptide Repeat Proteins but Not Neurodegeneration in BAC Transgenic Mice by Peters, Owen M., Cabrera, Gabriela Toro, Tran, Helene, Gendron, Tania F., McKeon, Jeanne E., Metterville, Jake, Weiss, Alexandra, Wightman, Nicholas, Salameh, Johnny, Kim, Juhyun, Sun, Huaming, Boylan, Kevin B., Dickson, Dennis, Kennedy, Zachary, Lin, Ziqiang, Zhang, Yong-Jie, Daughrity, Lillian, Jung, Chris, Gao, Fen-Biao, Bosco, Daryl A., Brown, Solange P., de Jong, Pieter, Petrucelli, Leonard, Mueller, Christian, Brown, Robert H., Horvitz, Howard Robert, Sapp, Peter C.

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Nicotine promotes neuron survival and partially protects from Parkinson’s disease by suppressing SIRT6 by Nicholatos, Justin W, Francisco, Adam B, Bender, Carolyn A, Yeh, Tiffany, Lugay, Fraz J, Salazar, Jairo E, Libert, Sergiy, Nicholatos, Justin W., Francisco, Adam B., Bender, Carolyn A., Lugay, Fraz J., Salazar, Jairo E., Glorioso, Christin A.

“…Inhibition of SIRT6 may be a promising strategy to ameliorate Parkinson’s and neurodegeneration. Keywords: Parkinson's disease; SIRT6; Nicotine; Neuroprotection; Neurodegeneration; Cell death…”
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Higher Vulnerability and Stress Sensitivity of Neuronal Precursor Cells Carrying an Alpha-Synuclein Gene Triplication by Flierl, Adrian, Oliveira, Luís M. A., Falomir-Lockhart, Lisandro J., Mak, Sally K., Hesley, Jayne, Soldner, Frank, Arndt-Jovin, Donna J., Jaenisch, Rudolf, Langston, J. William, Jovin, Thomas M., Schüle, Birgitt

“…Genetic predisposition, such as point mutations and copy number variants of the SNCA gene locus can cause very similar PD-like neurodegeneration. The impact of altered α-synuclein protein expression on integrity and developmental potential of neuronal stem cells is largely unexplored, but may have wide ranging implications for PD manifestation and disease progression. …”
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mTOR at the nexus of nutrition, growth, ageing and disease by Liu, Grace Y, Sabatini, David M

“…Given the pathway’s central role in maintaining cellular and physiological homeostasis, dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing. In this Review, we highlight recent advances in our understanding of the complex regulation of the mTOR pathway and discuss its function in the context of physiology, human disease and pharmacological intervention.…”
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mTOR Signaling in Growth Control and Disease by Laplante, Mathieu, Sabatini, David M., Sabatini, David

“…The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. …”
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Amyloid Deposits: Protection Against Toxic Protein Species? by Treusch, Sebastian, Cyr, Douglas M., Lindquist, Susan

“…Especially perplexing is the often poor correlation between protein deposits and other markers of neurodegeneration. As a result the question remains whether amyloid deposits are the disease causing species, the consequence of cellular disease pathology or even the result of a protective cellular response to misfolded protein species. …”
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Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model by Littleton, J. Troy, Zhang, Sheng, Saraswati, Sudipta, Feany, Mel B., Perrimon, Norbert

“…A polyglutamine expansion in the huntingtin (HTT) gene causes neurodegeneration in Huntington’s disease (HD), but the in vivo function of the native protein (Htt) is largely unknown. …”
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Programmed cell death-2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson’s disease by Fukae, Jiro, Sato, Shigeto, Shiba, Kahori, Sato, Ken-ichi, Mori, Hideo, Mizuno, Yoshikuni, Hattori, Nobutaka, Sharp, Phillip A.

“…Accumulation of its substrate may induce dopaminergic neurodegeneration in the substantia nigra (SN) of ARPD. …”
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Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics by Kuo, Szu-Yu, Castoreno, Adam B., Aldrich, Leslie N., Lassen, Kara G., Goel, Gautam, Dancik, Vlado, Kuballa, Petric, Latorre, Isabel, Conway, Kara L., Sarkar, Sovan, Maetzel, Dorothea, Jaenisch, Rudolf, Clemons, Paul A., Schreiber, Stuart L., Shamji, Alykhan F., Xavier, Ramnik J.

“…Studies of human genetics and pathophysiology have implicated the regulation of autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These findings have motivated the use of small-molecule probes to study how modulation of autophagy affects disease-associated phenotypes. …”
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Mitochondrial dysfunction remodels one-carbon metabolism in human cells by Bao, Xiaoyan Robert, Ong, Shao-En, Goldberger, Olga, Peng, Jun, Sharma, Rohit, Thompson, Dawn A, Vafai, Scott B, Cox, Andrew G, Marutani, Eizo, Ichinose, Fumito, Goessling, Wolfram, Carr, Steven A, Clish, Clary B, Mootha, Vamsi K, Regev, Aviv

“…Mitochondrial dysfunction is associated with a spectrum of human disorders, ranging from rare, inborn errors of metabolism to common, age-associated diseases such as neurodegeneration. How these lesions give rise to diverse pathology is not well understood, partly because their proximal consequences have not been well-studied in mammalian cells. …”
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Amino acids and mTORC1: from lysosomes to disease by Efeyan, Alejo, Zoncu, Roberto, Sabatini, David

“…The mechanistic target of rapamycin (mTOR) kinase controls growth and metabolism, and its deregulation underlies the pathogenesis of many diseases, including cancer, neurodegeneration, and diabetes. mTOR complex 1 (mTORC1) integrates signals arising from nutrients, energy, and growth factors, but how exactly these signals are propagated await to be fully understood. …”
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The biological function of the Huntingtin protein and its relevance to Huntington’s Disease pathology by Schulte, Joost, Littleton, J. Troy

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Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington’s disease by Yildirim, Ferah, Ng, Christopher, Kappes, Vincent, Ehrenberger, Tobias, Rigby, Siobhan K., Stivanello, Victoria, Gipson, Theresa A., Soltis, Anthony R., Vanhoutte, Peter, Caboche, Jocelyne, Housman, David E., Fraenkel, Ernest

“…Keywords: Huntington’s disease; neurodegeneration; transcriptional dysregulation; epigenomics; gene therapy…”
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Loss of Hsp70 Exacerbates Pathogenesis But Not Levels of Fibrillar Aggregates in a Mouse Model of Huntington's Disease by Lindquist, Susan, Steele, Andrew D., Wacker, Jennifer L., Huang, Shao-Yi, Aron, Rebecca, Lotz, Gregor P., Nguyen, QuangVu, Giorgini, Flaviano, Roberson, Erik D., Masliah, Eliezer, Muchowski, Paul J.

“…In contrast, deletion of Hsp70s did not accelerate disease in a mouse model of infectious prion-mediated neurodegeneration, ruling out the possibility that the Hsp70.1/70.3 mice are nonspecifically sensitized to all protein misfolding disorders. …”
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Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration by Horvitz, Howard Robert

“…These findings add to the growing body of evidence implicating the RNA processing pathway in neurodegeneration and suggest a critical role for ELP3 in neuron biology and of ELP3 variants in ALS.…”
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Huntingtin Aggregation Kinetics and Their Pathological Role in a Drosophila Huntington's Disease Model by Kimura, Yoko, Lee, Wyan-Ching Mimi, Littleton, J. Troy, Weiss, Kurt Richard

“…To examine the link between aggregation and neurodegeneration, we generated Drosophila melanogaster transgenic strains expressing fluorescently tagged human huntingtin encoding pathogenic (Q138) or nonpathogenic (Q15) proteins, allowing in vivo imaging of Huntingtin expression and aggregation in live animals. …”
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IKKβ slows Huntington’s disease progression in R6/1 mice by Ochaba, Joseph, Fote, Gianna, Kachemov, Marketta, Thein, Soe, Yeung, Sylvia Y., Lau, Alice L., Hernandez, Sarah, Lim, Ryan G., Casale, Malcolm, Neel, Michael J., Monuki, Edwin S., Reidling, Jack, Housman, David E, Thompson, Leslie M., Steffan, Joan S.

“…Notably, many striatal autophagy genes were up-regulated in HD vs. control mice; however, IKKβ knockout partially reduced this up-regulation in HD, increased striatal neurodegeneration, and enhanced an activated microglial response. …”
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Genetic and Chemical Correction of Cholesterol Accumulation and Impaired Autophagy in Hepatic and Neural Cells Derived from Niemann-Pick Type C Patient-Specific iPS Cells by Maetzel, Dorothea, Sarkar, Sovan, Wang, Haoyi, Abi-Mosleh, Lina, Xu, Ping, Gao, Qing, Mitalipova, Maisam, Jaenisch, Rudolf, Cheng, Albert Wu

“…Niemann-Pick type C (NPC) disease is a fatal inherited lipid storage disorder causing severe neurodegeneration and liver dysfunction with only limited treatment options for patients. …”
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