DNA Damage and Its Links to Neurodegeneration by Madabhushi, Ram, Pan, Ling, Tsai, Li-Huei

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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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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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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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S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration by Bhat, Vadiraja B., Seneviratnea, Uthpala, Nott, Alexi, Ravindra, Kodihalli C., 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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Walking the high wire: How neurons maintain stability in the crossline of neurodegeneration by Victor, Matheus B, Tsai, Li-Huei

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A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration by Graeff, Johannes, Kahn, Martin, Samiei, Alireza, Gao, Jun, Ota, Kristie, Rei, Damien, Tsai, Li-Huei

“…We found that in this model, CR significantly delayed the onset of neurodegeneration and synaptic loss and dysfunction, and thereby preserved cognitive capacities. …”
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Neurons burdened by DNA double-strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration by Welch, Gwyneth M, Boix, Carles A, Schmauch, Eloi, Davila-Velderrain, Jose, Victor, Matheus B, Dileep, Vishnu, Bozzelli, P Lorenzo, Su, Qiao, Cheng, Jemmie D, Lee, Audrey, Leary, Noelle S, Pfenning, Andreas R, Kellis, Manolis, Tsai, Li-Huei

“…<jats:p>DNA double-strand breaks (DSBs) are linked to neurodegeneration and senescence. However, it is not clear how DSB-bearing neurons influence neuroinflammation associated with neurodegeneration. …”
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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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Mechanisms of DNA double strand break-mediated neurotoxicity in neurodegenerative disease by Welch, Gwyneth M.

“…DNA double strand breaks (DSBs) are also linked to neurodegeneration and senescence. However, it is not clear how DSB-bearing neurons influence processes of neuroinflammation and neurodegeneration. …”
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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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Telomerase reverse transcriptase preserves neuron survival and cognition in Alzheimer’s disease models by Shim, Hong Seok, Horner, James W, Wu, Chang-Jiun, Li, Jiexi, Lan, Zheng D, Jiang, Shan, Xu, Xueping, Hsu, Wen-Hao, Zal, Tomasz, Flores, Ivonne I, Deng, Pingna, Lin, Yuan-Ta, Tsai, Li-Huei, Wang, Y Alan, DePinho, Ronald A

“…Amyloid-induced neurodegeneration plays a central role in Alzheimer's disease (AD) pathogenesis. …”
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A Developmental Switch in Microglial HDAC Function by Mathys, Hansruedi, Penney, Jay, Tsai, Li-Huei

“…In this issue of Immunity, Datta et al. (2018) uncover surprising and distinct effects of deleting the epigenetic regulators HDAC1 and HDAC2 during microglial development versus during the course of neurodegeneration.…”
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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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Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection by Adaikkan, Chinnakkaruppan, Middleton, Steven J, Marco, Asaf, Pao, Ping-Chieh, Mathys, Hansruedi, Kim, David Nam-Woo, Gao, Fan, Young, Jennie Z, Suk, Ho-Jun, Boyden, Edward S, McHugh, Thomas J, Tsai, Li-Huei

“…Chronic application of patterned visual stimulation in neurodegeneration mouse models to entrain gamma oscillations results in preservation of neuronal and synaptic density across multiple brain regions.…”
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3D mapping reveals network-specific amyloid progression and subcortical susceptibility in mice by Gail Canter, Rebecca, Huang, Wen-Chin, Choi, Heejin, Wang, Jun, Ashley Watson, Lauren, Yao, Christine G, Abdurrob, Fatema, Bousleiman, Stephanie M, Young, Jennie Z, Bennett, David A, Delalle, Ivana, Chung, Kwanghun, Tsai, Li-Huei

“…Prominent hypotheses suggest accumulation of beta-amyloid (Aβ) contributes to neurodegeneration and memory loss, however identifying brain regions with early susceptibility to Aβ remains elusive. …”
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Building in vitro models of the brain to understand the role of APOE in Alzheimer’s disease by Pinals, Rebecca L, Tsai, Li-Huei

“…Such models have delivered crucial insights into cellular mechanisms and cell type–specific roles underlying the perturbed biological functions that trigger pathogenic cascades and propagate neurodegeneration. Collectively, hiPSC-based models are envisioned to be an impactful platform for uncovering fundamental AD understanding, with high translational value toward AD drug discovery and testing.…”
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HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease by Pao, Ping-Chieh, Patnaik, Debasis, Watson, L Ashley, Gao, Fan, Pan, Ling, Wang, Jun, Adaikkan, Chinnakkaruppan, Penney, Jay, Cam, Hugh P, Huang, Wen-Chin, Pantano, Lorena, Lee, Audrey, Nott, Alexi, Phan, Trongha X, Gjoneska, Elizabeta, Elmsaouri, Sara, Haggarty, Stephen J, Tsai, Li-Huei

“…Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration.…”
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