An epigenetic blockade of cognitive functions in the neurodegenerating brain by Rei, Damien, Guan, Ji-Song, Wang, Wen-Yuan, Seo, Jinsoo, Hennig, Krista M., Nieland, Thomas J., Fass, Daniel M., Kao, Patricia F., Kahn, Martin, Su, Susan C., Samiei, Alireza, Joseph, Nadine, Haggarty, Stephen J., Delalle, Ivana, Tsai, Li-Huei, Graff, Johannes

“…Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. …”
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Linking Cell Cycle Reentry and DNA Damage in Neurodegeneration by Kim, Dohoon, Tsai, Li-Huei

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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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S-nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration by Bhat, Vadiraja B., Seneviratne, Uthpala Indrajith, Nott, Alexander, Kodihalli, Ravindra, Wishnok, John S, Tsai, Li-Huei, Tannenbaum, Steven R

“…SNOTRAP identified 313 endogenous SNO-sites in 251 proteins in the mouse brain, of which 135 SNO-proteins were detected only during neurodegeneration. S-nitrosation in the brain shows regional differences and becomes elevated during early stages of neurodegeneration in the CK-p25 mouse. …”
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Synaptic Deficits Are Rescued in the p25/Cdk5 Model of Neurodegeneration by the Reduction of beta-Secretase (BACE1) by Giusti-Rodriguez, Paola, Gao, Jun, Graff, Johannes, Rei, Damien, Soda, Takahiro, Tsai, Li-Huei

“…These findings explore the impact of targeting Aβ production in a mouse model of neurodegeneration and cognitive impairment, and how this may translate into therapeutic approaches for sporadic AD.…”
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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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Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease by Gjoneska, Elizabeta, Pfenning, Andreas R., Mathys, Hansruedi, Quon, Gerald, Kundaje, Anshul, Tsai, Li-Huei, Kellis, Manolis

“…Several genes have been implicated in AD, but chromatin state alterations during neurodegeneration remain uncharacterized. Here we profile transcriptional and chromatin state dynamics across early and late pathology in the hippocampus of an inducible mouse model of AD-like neurodegeneration. …”
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SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons by Dobbin, Matthew M., Madabhushi, Ram, Pan, Ling, Chen, Yue, Kim, Dohoon, Gao, Jun, Ahanonu, Biafra, Pao, Ping-Chieh, Qiu, Yi, Zhao, Yingming, Tsai, Li-Huei

“…HDAC1 mutations that mimic a constitutively acetylated state rendered neurons more susceptible to DNA damage, whereas pharmacological SIRT1 activators that promoted HDAC1 deacetylation also reduced DNA damage in two mouse models of neurodegeneration. We propose that SIRT1 is an apical transducer of the DSB response and that SIRT1 activation offers an important therapeutic avenue in neurodegeneration.…”
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The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner by Kisby, Glen E., Fry, Rebecca C., Lasarev, Michael R., Bammler, Theodor K., Beyer, Richard P., Churchwell, Mona, Doerge, Daniel R., Meira, Lisiane B., Palmer, Valerie S., Ramos-Crawford, Ana-Luiza, Ren, Xuefeng, Sullivan, Robert C., Kavanagh, Terrance J., Samson, Leona D., Zarbl, Helmut, Spencer, Peter S.

“…These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). …”
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Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death by Jinde, Seiichiro, Belforte, Juan E., Yamamoto, Jun, Wilson, Matthew A., Tonegawa, Susumu, Nakazawa, Kazu

“…Consequently, on subsequent days, mutants manifested prolonged epileptiform activity and massive neurodegeneration of CA1 cells, including local GABAergic neurons. …”
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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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Transient enhancement of proliferation of neural progenitors and impairment of their long-term survival in p25 transgenic mice by Zou, Donghua, Zhou, Yijing, Liu, Long, Dong, Fengping, Shu, Tianzhi, Zhou, Ying, Tsai, Li-Huei, Mao, Yingwei

“…We aimed to determine the role of p25-mediated neurodegeneration on neurogenesis in an inducible transgenic mouse line overexpressing p25 (p25 TG) in the forebrain. …”
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Potential for Transcranial Laser or LED Therapy to Treat Stroke, Traumatic Brain Injury, and Neurodegenerative Disease by Naeser, Margaret A., Hamblin, Michael R.

“…The basic biochemical pathways activated by NIR light, e.g., increased adenosine-5’-triphosphate (ATP) production, and signaling pathways activated by reactive oxygen species, nitric oxide release, and increased cyclic adenosine monophosphate (AMP) all work together to produce beneficial effects in brains whose function has been compromised by ischemia, traumatic injury, or neurodegeneration. One of the main mechanisms of action of transcranial light therapy (TLT) is to prevent neurons from dying, when they have been subjected to some sort of hypoxic, traumatic, or toxic insult. …”
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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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Extracellular Acidic pH Inhibits Oligodendrocyte Precursor Viability, Migration, and Differentiation by Jagielska, Anna, Wilhite, Kristen D., Van Vliet, Krystyn J.

“…Failure of this repair process is characteristic of neurodegeneration in demyelinating diseases such as multiple sclerosis, and it remains unclear how the lesion microenvironment contributes to decreased remyelination potential of oligodendrocytes. …”
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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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