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In our laboratory, we seek to elucidate the mechanisms underlying the actions of genetic polymorphisms that modulate the risk of disease, especially Alzheimer’s disease (AD). Our goal is to translate these findings into novel approaches to prevent or treat human disease. We are primarily focused on AD genetics because genetic risk factors drive the majority of AD risk. Also, since genetic variants modulate AD risk, then by definition, drugs that act similarly will also modulate AD risk. Hence, we interpret the pathways identified by genetics as validated drug targets.
Our experimental approach begins by noting that high throughput genome wide association studies have identified a series of single nucleotide polymorphisms (SNP)s that are robustly associated with AD risk. Hence our goal is to perform molecular genetic studies to identify the mechanisms of action underlying these SNPs. The primary actions of these SNPs, or their co-inherited proxy SNPs, are to (i) alter amino acid sequence, (ii) alter gene expression or (iii) alter mRNA splicing. For each of the AD-associated SNPs, we are working through the process of determining the molecular impact of the SNP. For example, a CD33 SNP has been associated with AD risk. We found that this SNP acts through a co-inherited proxy SNP to modulate the splicing efficiency of the second exon in CD33. The allele that protects from AD risk reduces the inclusion of exon 2. The CD33 isoform lacking exon 2 is predicted to produce a non-functional CD33. Hence, our findings suggest that reducing CD33 function protects from AD risk. We are currently pursuing this hypothesis at multiple levels, including the study of CD33 inhibitors.
Overall, our work is facilitated by our association with the Sanders-Brown Center on Aging and its Alzheimer's Disease Center (ADC). Our ADC has been critical in providing hundreds of DNA samples from well-characterized AD and control individuals, which are necessary for genotyping polymorphisms, as well as autopsy-derived CSF and brain samples, which has allowed us to quantify the levels of the gene products and genetic variant proteins of interest in a rapid and human-disease relevant fashion. We have similar projects that focus upon other AD-related polymorphisms, as well as pilot studies to evaluate the actions of polymorphisms that modulate the risk of multiple sclerosis, migraine, and ALS.
In summary, the overall goal of our laboratory is to use human genetics to identify molecular mechanisms that modulate the risk of human disease, especially AD. These studies contribute to the fight against AD by identifying individuals at risk, identifying possible novel therapies, and tailoring therapy to responsive individuals.
2018-2023 1R25GM125680-01 “Interactive Mentoring to Enhance Research Skills (IMERS)”
D. Frazier, PI, S. Estus, co-I
2018-2019 NIH R56AG057589. “The surprising impact of APOE alleles on gut microbiome:
does altering the microbiome reduce AD risk?” S. Estus, PI
2018-2023 NIH RF1AG059717. “Translating SHIP1 genetics to generate a novel
Alzheimer's pharmacologic agent” S. Estus, M.B. Humphrey, and W.G. Kerr
Malik M, Chiles J 3rd, Xi HS, Medway C, Simpson J, Potluri S, Howard D, Liang Y, Paumi CM, Mukherjee S, Crane P, Younkin S, Fardo DW, Estus S. Genetics of CD33 in Alzheimer's Disease and Acute Myeloid Leukemia Hum Mol Genet. 24:3557-3570 (2015). PMC4498153
Malik M, Parikh I, Vasquez JB, Smith C, Tai L, Bu G, LaDu MJ, Fardo DW, Rebeck GW, Estus S. Genetics ignite focus on microglial inflammation in Alzheimer's disease. Mol Neurodegener. 10:52 (2015). PMC4595327
Qi Gan W, Estus S, Smith JH. Association between overall and mentholated cigarette smoking with headache in a nationally representative sample. Headache 56(3):511-8. (2016). PMID: 26926358
Kang SS, Kurti A, Wojtas A, Baker KE, Liu CC, Kanekiyo T, Deming Y, Cruchaga C, Estus S, Bu G, Fryer JD. Identification of plexin A4 as a novel clusterin receptor links two Alzheimer's disease risk genes. Hum Mol Genet. 25(16):3467-3475. (2016) PMC5179943
De Rossi P, Buggia-Prévot V, Clayton BL, Vasquez JB, van Sanford C, Andrew RJ, Lesnick R, Botté A, Deyts C, Salem S, Rao E, Rice RC, Parent A, Kar S, Popko B, Pytel P, Estus S, Thinakaran G. Predominant expression of Alzheimer's disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts. Mol Neurodegener. 11(1):59 (2016) PMC4973113.
Vasquez JB, Simpson JF, Harpole R, Estus S. Alzheimer's Disease Genetics and ABCA7 Splicing. J Alzheimers Dis. 59:633-641 (2017) PMC28655137.
Katsumata Y, Nelson PT, Estus S; Alzheimer's Disease Neuroimaging Initiative (ADNI), Fardo DW. Translating Alzheimer's disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs. Neurobiol Aging. 74:135-146 (2018). PMID:30448613
Estus S, Shaw BC, Devanney N, Katsumata Y, Press EE, Fardo DW. Evaluation of CD33 as a genetic risk factor for Alzheimer's disease. Acta Neuropathol. 2019 Aug;138(2):187-199.PMID: 30949760
Katsumata Y, Fardo DW, Bachstetter AD, Artiushin SC, Wang WX, Wei A, Brzezinski LJ, Nelson BG, Huang Q, Abner EL, Anderson S, Patel I, Shaw BC, Price DA, Niedowicz, DM, Wilcock DW, Jicha GA, Neltner JH, Van Eldik LJ, Estus S, and Nelson PT. Alzheimer’s disease pathology-associated polymorphism in a complex variable number of tandem repeat region within the MUC6 gene, near the AP2A2 gene. Neuropathol Exp Neurol. 2020 Jan 1;79(1):3-21. PMID:31748784
Maldonado Weng J, Parikh I, Naqib A, York J, Green SJ, Estus S, LaDu MJ. Synergistic effects of APOE and sex on the gut microbiome of young EFAD transgenic mice. Mol Neurodegener. 2019 Dec 20;14(1):47. PMID: 31861986
Parikh IJ, Estus JL, Zajac DJ, Malik M, Maldonado Weng J, Tai LM, Chlipala GE, LaDu MJ, Green SJ, Estus S. Murine Gut Microbiome Association With APOE Alleles. Front Immunol. 2020;11:200. PMID: 32117315
Smith JL, Estus S, Lennie TA, Moser DK, Chung ML, Mudd-Martin G. TAS2R38 PAV Haplotype Predicts Vegetable Consumption in Community-Dwelling Caucasian Adults at Risk for Cardiovascular Disease. Biol Res Nurs. 2020 Mar 24: PMID: 32207317
- Smith, JL ; Mudd-Martin, G.; Estus, S.; Lennie, TA ; Chung, ML "TAS2R38 Haplotype Predicts 24-Hour Urinary Sodium Excretion in Patients With Heart Failure and Their Family Caregivers." The Journal of cardiovascular nursing (2020): [PubMed Link] | [ Full text ]
- Smith, JL ; Estus, S.; Lennie, TA ; Moser, DK ; Chung, ML ; Mudd-Martin, G. "<i>TAS2R38</i> PAV Haplotype Predicts Vegetable Consumption in Community-Dwelling Caucasian Adults at Risk for Cardiovascular Disease." Biological research for nursing 22, 3 (2020): 326-333. [PubMed Link] | [ Full text ]
- Katsumata, Y.; Fardo, DW ; Bachstetter, AD ; Artiushin, SC ; Wang, WX ; Wei, A.; Brzezinski, LJ ; Nelson, BG ; Huang, Q.; Abner, EL ; Anderson, S.; Patel, I ; Shaw, BC ; Price, DA ; Niedowicz, DM ; Wilcock, DW ; Jicha, GA ; Neltner, JH ; Van Eldik, LJ ; Estus, S.; Nelson, PT "Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene." Journal of neuropathology and experimental neurology 79, 1 (2020): 3-21. [PubMed Link] | [ Full text ]
- Parikh, IJ ; Estus, JL ; Zajac, DJ ; Malik, M.; Weng, Maldonado ; Tai, LM ; Chlipala, GE ; LaDu, MJ ; Green, SJ ; Estus, S. "Murine Gut Microbiome Association With <i>APOE</i> Alleles." Frontiers in immunology 11, (2020): 200. [PubMed Link] | [ Full text ]
- Katsumata, Y.; Nelson, PT ; Estus, S.; Alzheimer's Disease Neuroimaging Initiative, (ADNI). ; Fardo, DW "Translating Alzheimer's disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs." Neurobiology of aging 74, (2019): 135-146. [PubMed Link] | [ Full text ]
- Weng, Maldonado ; Parikh, I.; Naqib, A ; York, J.; Green, SJ ; Estus, S.; LaDu, MJ "Synergistic effects of APOE and sex on the gut microbiome of young EFAD transgenic mice." Molecular neurodegeneration 14, 1 (2019): 47. [PubMed Link] | [ Full text ]
- Estus, S.; Shaw, BC ; Devanney, N ; Katsumata, Y.; Press, EE ; Fardo, DW "Evaluation of CD33 as a genetic risk factor for Alzheimer's disease." Acta neuropathologica 138, 2 (2019): 187-199. [PubMed Link] | [ Full text ]
- Vasquez, JB ; Simpson, JF ; Harpole, R.; Estus, S. "Alzheimer's Disease Genetics and ABCA7 Splicing." Journal of Alzheimer's disease : JAD 59, 2 (2017): 633-641. [PubMed Link] | [ Full text ]
- Chester, DS ; DeWall, CN ; Derefinko, KJ ; Estus, S.; Lynam, DR ; Peters, JR ; Jiang, Y. "Looking for reward in all the wrong places: dopamine receptor gene polymorphisms indirectly affect aggression through sensation-seeking." Social neuroscience 11, 5 (2016): 487-94. [PubMed Link] | [ Full text ]
- Gan, WQ ; Estus, S.; Smith, JH "Association Between Overall and Mentholated Cigarette Smoking With Headache in a Nationally Representative Sample." Headache 56, 3 (2016): 511-8. [PubMed Link] | [ Full text ]
- De Rossi, P.; Buggia-Prévot, V.; Clayton, BL ; Vasquez, JB ; Sanford, C.; Andrew, RJ ; Lesnick, R.; Botté, A.; Deyts, C.; Salem, S.; Rao, E.; Rice, RC ; Parent, A.; Kar, S.; Popko, B.; Pytel, P.; Estus, S.; Thinakaran, G. "Predominant expression of Alzheimer's disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts." Molecular neurodegeneration 11, 1 (2016): 59. [PubMed Link] | [ Full text ]
- Kang, SS ; Kurti, A.; Wojtas, A.; Baker, KE ; Liu, CC ; Kanekiyo, T.; Deming, Y.; Cruchaga, C.; Estus, S.; Bu, G.; Fryer, JD "Identification of plexin A4 as a novel clusterin receptor links two Alzheimer's disease risk genes." Human molecular genetics 25, 16 (2016): 3467-3475. [PubMed Link] | [ Full text ]
- Malik, M.; Parikh, I.; Vasquez, JB ; Smith, C.; Tai, L.; Bu, G.; LaDu, MJ ; Fardo, DW ; Rebeck, GW ; Estus, S. "Genetics ignite focus on microglial inflammation in Alzheimer's disease." Molecular neurodegeneration 10, (2015): 52. [PubMed Link] | [ Full text ]
- Malik, M.; Chiles J, 3rd ; Xi, HS ; Medway, C.; Simpson, J.; Potluri, S.; Howard, D.; Liang, Y.; Paumi, CM ; Mukherjee, S.; Crane, P.; Younkin, S.; Fardo, DW ; Estus, S. "Genetics of CD33 in Alzheimer's disease and acute myeloid leukemia." Human molecular genetics 24, 12 (2015): 3557-70. [PubMed Link] | [ Full text ]
- Chester, DS ; DeWall, CN ; Derefinko, KJ ; Estus, S.; Peters, JR ; Lynam, DR ; Jiang, Y. "Monoamine oxidase A (MAOA) genotype predicts greater aggression through impulsive reactivity to negative affect." Behavioural brain research 283, (2015): 97-101. [PubMed Link] | [ Full text ]
- Downer, B.; Estus, S.; Katsumata, Y.; Fardo, DW "Longitudinal trajectories of cholesterol from midlife through late life according to apolipoprotein E allele status." International journal of environmental research and public health 11, 10 (2014): 10663-93. [PubMed Link] | [ Full text ]
- Liu, CC ; Tsai, CW ; Deak, F.; Rogers, J.; Penuliar, M.; Sung, YM ; Maher, JN ; Fu, Y.; Li, X.; Xu, H.; Estus, S.; Hoe, HS ; Fryer, JD ; Kanekiyo, T.; Bu, G. "Deficiency in LRP6-mediated Wnt signaling contributes to synaptic abnormalities and amyloid pathology in Alzheimer's disease." Neuron 84, 1 (2014): 63-77. [PubMed Link] | [ Full text ]
- Gold, BT ; Zhu, Z.; Brown, CA ; Andersen, AH ; LaDu, MJ ; Tai, L.; Jicha, GA ; Kryscio, RJ ; Estus, S.; Nelson, PT ; Scheff, SW ; Abner, E.; Schmitt, FA ; Van Eldik, LJ ; Smith, CD "White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults." Neurobiology of aging 35, 10 (2014): 2263-71. [PubMed Link] | [ Full text ]
- Tai, LM ; Mehra, S.; Shete, V.; Estus, S.; Rebeck, GW ; Bu, G.; LaDu, MJ "Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk." Molecular neurodegeneration 9, (2014): 2. [PubMed Link] | [ Full text ]
- Parikh, I.; Medway, C.; Younkin, S.; Fardo, DW ; Estus, S. "An intronic PICALM polymorphism, rs588076, is associated with allelic expression of a PICALM isoform." Molecular neurodegeneration 9, (2014): 32. [PubMed Link] | [ Full text ]
- Parikh, I.; Fardo, DW ; Estus, S. "Genetics of PICALM expression and Alzheimer's disease." PloS one 9, 3 (2014): e91242. [PubMed Link] | [ Full text ]
- Nelson, PT ; Estus, S.; Abner, EL ; Parikh, I.; Malik, M.; Neltner, JH ; Ighodaro, E.; Wang, WX ; Wilfred, BR ; Wang, LS ; Kukull, WA ; Nandakumar, K.; Farman, ML ; Poon, WW ; Corrada, MM ; Kawas, CH ; Cribbs, DH ; Bennett, DA ; Schneider, JA ; Larson, EB ; Crane, PK ; Valladares, O.; Schmitt, FA ; Kryscio, RJ ; Jicha, GA ; Smith, CD ; Scheff, SW ; Sonnen, JA ; Haines, JL ; Pericak-Vance, MA ; Mayeux, R.; Farrer, LA ; Van Eldik, LJ ; Horbinski, C.; Green, RC ; Gearing, M.; Poon, LW ; Kramer, PL ; Woltjer, RL ; Montine, TJ ; Partch, AB ; Rajic, AJ ; Richmire, K.; Monsell, SE ; Alzheimer’ Disease Genetic, Consortium. ; Schellenberg, GD ; Fardo, DW "ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology." Acta neuropathologica 127, 6 (2014): 825-43. [PubMed Link] | [ Full text ]
- Vasquez, JB ; Fardo, DW ; Estus, S. "ABCA7 expression is associated with Alzheimer's disease polymorphism and disease status." Neuroscience letters 556, (2013): 58-62. [PubMed Link] | [ Full text ]
- Nelson, PT ; Pious, NM ; Jicha, GA ; Wilcock, DM ; Fardo, DW ; Estus, S.; Rebeck, GW "APOE-ε2 and APOE-ε4 correlate with increased amyloid accumulation in cerebral vasculature." Journal of neuropathology and experimental neurology 72, 7 (2013): 708-15. [PubMed Link] | [ Full text ]
- Tai, LM ; Bilousova, T.; Jungbauer, L.; Roeske, SK ; Youmans, KL ; Yu, C.; Poon, WW ; Cornwell, LB ; Miller, CA ; Vinters, HV ; Van Eldik, LJ ; Fardo, DW ; Estus, S.; Bu, G.; Gylys, KH ; LaDu, MJ "Levels of soluble apolipoprotein E/amyloid-β (Aβ) complex are reduced and oligomeric Aβ increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples." The Journal of biological chemistry 288, 8 (2013): 5914-26. [PubMed Link] | [ Full text ]
- Malik, M.; Simpson, JF ; Parikh, I.; Wilfred, BR ; Fardo, DW ; Nelson, PT ; Estus, S. "CD33 Alzheimer's risk-altering polymorphism, CD33 expression, and exon 2 splicing." The Journal of neuroscience : the official journal of the Society for Neuroscience 33, 33 (2013): 13320-5. [PubMed Link] | [ Full text ]
- Holler, CJ ; Webb, RL ; Laux, AL ; Beckett, TL ; Niedowicz, DM ; Ahmed, RR ; Liu, Y.; Simmons, CR ; Dowling, AL ; Spinelli, A.; Khurgel, M.; Estus, S.; Head, E.; Hersh, LB ; Murphy, MP "BACE2 expression increases in human neurodegenerative disease." The American journal of pathology 180, 1 (2012): 337-50. [PubMed Link] | [ Full text ]
- Youmans, KL ; Tai, LM ; Nwabuisi-Heath, E.; Jungbauer, L.; Kanekiyo, T.; Gan, M.; Kim, J.; Eimer, WA ; Estus, S.; Rebeck, GW ; Weeber, EJ ; Bu, G.; Yu, C.; LaDu, MJ "APOE4-specific changes in Aβ accumulation in a new transgenic mouse model of Alzheimer disease." The Journal of biological chemistry 287, 50 (2012): 41774-86. [PubMed Link] | [ Full text ]
- Ling, IF ; Bhongsatiern, J.; Simpson, JF ; Fardo, DW ; Estus, S. "Genetics of clusterin isoform expression and Alzheimer's disease risk." PloS one 7, 4 (2012): e33923. [PubMed Link] | [ Full text ]
- Smith, JD ; Moylan, JS ; Hardin, BJ ; Chambers, MA ; Estus, S.; Telling, GC ; Reid, MB "Prion protein expression and functional importance in skeletal muscle." Antioxidants & redox signaling 15, 9 (2011): 2465-75. [PubMed Link] | [ Full text ]
- Simmons, CR ; Zou, F.; Younkin, SG ; Estus, S. "Rheumatoid arthritis-associated polymorphisms are not protective against Alzheimer's disease." Molecular neurodegeneration 6, (2011): 33. [PubMed Link] | [ Full text ]
- Burchett, ME ; Ling, IF ; Estus, S. "FBN1 isoform expression varies in a tissue and development-specific fashion." Biochemical and biophysical research communications 411, 2 (2011): 323-8. [PubMed Link] | [ Full text ]
- Simmons, CR ; Zou, F.; Younkin, SG ; Estus, S. "Evaluation of the global association between cholesterol-associated polymorphisms and Alzheimer's disease suggests a role for rs3846662 and HMGCR splicing in disease risk." Molecular neurodegeneration 6, (2011): 62. [PubMed Link] | [ Full text ]
- Dieter, LS ; Estus, S. "Isoform of APOE with retained intron 3; quantitation and identification of an associated single nucleotide polymorphism." Molecular neurodegeneration 5, (2010): 34. [PubMed Link] | [ Full text ]
- Ling, IF ; Gopalraj, RK ; Simpson, JF ; Estus, S. "Expression and regulation of a low-density lipoprotein receptor exon 12 splice variant." Journal of neurochemistry 115, 3 (2010): 614-24. [PubMed Link] | [ Full text ]
- Ling, IF ; Estus, S. "Role of SFRS13A in low-density lipoprotein receptor splicing." Human mutation 31, 6 (2010): 702-9. [PubMed Link] | [ Full text ]
- Grear, KE ; Ling, IF ; Simpson, JF ; Furman, JL ; Simmons, CR ; Peterson, SL ; Schmitt, FA ; Markesbery, WR ; Liu, Q.; Crook, JE ; Younkin, SG ; Bu, G.; Estus, S. "Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain." Molecular neurodegeneration 4, (2009): 46. [PubMed Link] | [ Full text ]
- Liu, Q.; Zhang, J.; Tran, H.; Verbeek, MM ; Reiss, K.; Estus, S.; Bu, G. "LRP1 shedding in human brain: roles of ADAM10 and ADAM17." Molecular neurodegeneration 4, (2009): 17. [PubMed Link] | [ Full text ]
- Zhu, H.; Taylor, JW ; Bennett, DA ; Younkin, SG ; Estus, S. "Lack of association of hepatic lipase polymorphisms with late-onset Alzheimer's disease." Neurobiology of aging 29, 5 (2008): 793-4. [PubMed Link] | [ Full text ]
- Zou, F.; Gopalraj, RK ; Lok, J.; Zhu, H.; Ling, IF ; Simpson, JF ; Tucker, HM ; Kelly, JF ; Younkin, SG ; Dickson, DW ; Petersen, RC ; Graff-Radford, NR ; Bennett, DA ; Crook, JE ; Younkin, SG ; Estus, S. "Sex-dependent association of a common low-density lipoprotein receptor polymorphism with RNA splicing efficiency in the brain and Alzheimer's disease." Human molecular genetics 17, 7 (2008): 929-35. [PubMed Link] | [ Full text ]
- Zhu, H.; Tucker, HM ; Grear, KE ; Simpson, JF ; Manning, AK ; Cupples, LA ; Estus, S. "A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol." Human molecular genetics 16, 14 (2007): 1765-72. [PubMed Link] | [ Full text ]
- Tangpong, J.; Cole, MP ; Sultana, R.; Estus, S.; Vore, M.; St Clair, W.; Ratanachaiyavong, S.; St Clair, DK ; Butterfield, DA "Adriamycin-mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain." Journal of neurochemistry 100, 1 (2007): 191-201. [PubMed Link] | [ Full text ]
- Rebeck, GW ; LaDu, MJ ; Estus, S.; Bu, G.; Weeber, EJ "The generation and function of soluble apoE receptors in the CNS." Molecular neurodegeneration 1, (2006): 15. [PubMed Link] | [ Full text ]
- Tangpong, J.; Cole, MP ; Sultana, R.; Joshi, G.; Estus, S.; Vore, M.; St Clair, W.; Ratanachaiyavong, S.; St Clair, DK ; Butterfield, DA "Adriamycin-induced, TNF-alpha-mediated central nervous system toxicity." Neurobiology of disease 23, 1 (2006): 127-39. [PubMed Link] | [ Full text ]
- Joshi, G.; Sultana, R.; Tangpong, J.; Cole, MP ; St Clair, DK ; Vore, M.; Estus, S.; Butterfield, DA "Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain." Free radical research 39, 11 (2005): 1147-54. [PubMed Link] | [ Full text ]
- Gopalraj, RK ; Zhu, H.; Kelly, JF ; Mendiondo, M.; Pulliam, JF ; Bennett, DA ; Estus, S. "Genetic association of low density lipoprotein receptor and Alzheimer's disease." Neurobiology of aging 26, 1 (2005): 1-7. [PubMed Link] | [ Full text ]
- Ertekin-Taner, N.; Ronald, J.; Feuk, L.; Prince, J.; Tucker, M.; Younkin, L.; Hella, M.; Jain, S.; Hackett, A.; Scanlin, L.; Kelly, J.; Kihiko-Ehman, M.; Neltner, M.; Hersh, L.; Kindy, M.; Markesbery, W.; Hutton, M.; Andrade, M.; Petersen, RC ; Graff-Radford, N.; Estus, S.; Brookes, AJ ; Younkin, SG "Elevated amyloid beta protein (Abeta42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator gene." Human molecular genetics 14, 3 (2005): 447-60. [PubMed Link] | [ Full text ]
- Tucker, HM ; Simpson, J.; Kihiko-Ehmann, M.; Younkin, LH ; McGillis, JP ; Younkin, SG ; Degen, JL ; Estus, S. "Plasmin deficiency does not alter endogenous murine amyloid beta levels in mice." Neuroscience letters 368, 3 (2004): 285-9. [PubMed Link] | [ Full text ]
- McCollum, AT ; Estus, S. "NGF acts via p75 low-affinity neurotrophin receptor and calpain inhibition to reduce UV neurotoxicity." Journal of neuroscience research 77, 4 (2004): 552-64. [PubMed Link] | [ Full text ]
- Bruckner, SR ; Perry, G.; Estus, S. "4-hydroxynonenal contributes to NGF withdrawal-induced neuronal apoptosis." Journal of neurochemistry 85, 4 (2003): 999-1005. [PubMed Link] | [ Full text ]
- Whitaker, C.; Eckman, C.; Almeida, C.; Feinstein, D.; Atwood, C.; Eckman, E.; Crutcher, K.; Hersh, L.; Leissring, M.; LaVoie, M.; Ertekin-Taner, N.; Shapiro, P.; Takahashi, R.; Yamin, R.; Mansourian, S.; Estus, S.; Lesné, S.; Turner, T.; Farris, W.; Stroebel, G. "Live discussion: Amyloid-beta degradation: the forgotten half of Alzheimer's disease. 12 September 2002." Journal of Alzheimer's disease : JAD 5, 6 (2003): 491-7. [PubMed Link] | [ Full text ]
- Bu, J.; Bruckner, SR ; Sengoku, T.; Geddes, JW ; Estus, S. "Glutamate regulates caveolin expression in rat hippocampal neurons." Journal of neuroscience research 72, 2 (2003): 185-90. [PubMed Link] | [ Full text ]
- McCollum, AT ; Nasr, P.; Estus, S. "Calpain activates caspase-3 during UV-induced neuronal death but only calpain is necessary for death." Journal of neurochemistry 82, 5 (2002): 1208-20. [PubMed Link] | [ Full text ]
- Tucker, HM ; Kihiko-Ehmann, M.; Estus, S. "Urokinase-type plasminogen activator inhibits amyloid-beta neurotoxicity and fibrillogenesis via plasminogen." Journal of neuroscience research 70, 2 (2002): 249-55. [PubMed Link] | [ Full text ]
- Estus, S.; Borchelt, D.; Kindy, MS ; Vassar, R. "Abeta deposition is essential to AD neuropathology." Journal of Alzheimer's disease : JAD 4, 3 (2002): 133-8. [PubMed Link] | [ Full text ]
- Bruckner, SR ; Estus, S. "JNK3 contributes to c-jun induction and apoptosis in 4-hydroxynonenal-treated sympathetic neurons." Journal of neuroscience research 70, 5 (2002): 665-70. [PubMed Link] | [ Full text ]
- Bruckner, SR ; Tammariello, SP ; Kuan, CY ; Flavell, RA ; Rakic, P.; Estus, S. "JNK3 contributes to c-Jun activation and apoptosis but not oxidative stress in nerve growth factor-deprived sympathetic neurons." Journal of neurochemistry 78, 2 (2001): 298-303. [PubMed Link] | [ Full text ]
- Dhillon, HS ; Dong, GX ; Yurek, DM ; Estus, S.; Rangnekar, VM ; Dendle, P.; Prasad, RM "Regional expression of Par-4 mRNA and protein after fluid percussion brain injury in the rat." Experimental neurology 170, 1 (2001): 140-8. [PubMed Link] | [ Full text ]
- Wu, HJ ; Venkataraman, C.; Estus, S.; Dong, C.; Davis, RJ ; Flavell, RA ; Bondada, S. "Positive signaling through CD72 induces mitogen-activated protein kinase activation and synergizes with B cell receptor signals to induce X-linked immunodeficiency B cell proliferation." Journal of immunology (Baltimore, Md. : 1950) 167, 3 (2001): 1263-73. [PubMed Link] | [ Full text ]
- Tucker, HM ; Kihiko-Ehmann, M.; Wright, S.; Rydel, RE ; Estus, S. "Tissue plasminogen activator requires plasminogen to modulate amyloid-beta neurotoxicity and deposition." Journal of neurochemistry 75, 5 (2000): 2172-7. [PubMed Link] | [ Full text ]
- Tucker, HM ; Kihiko, M.; Caldwell, JN ; Wright, S.; Kawarabayashi, T.; Price, D.; Walker, D.; Scheff, S.; McGillis, JP ; Rydel, RE ; Estus, S. "The plasmin system is induced by and degrades amyloid-beta aggregates." The Journal of neuroscience : the official journal of the Society for Neuroscience 20, 11 (2000): 3937-46. [PubMed Link] | [ Full text ]
- Tammariello, SP ; Quinn, MT ; Estus, S. "NADPH oxidase contributes directly to oxidative stress and apoptosis in nerve growth factor-deprived sympathetic neurons." The Journal of neuroscience : the official journal of the Society for Neuroscience 20, 1 (2000): RC53. [PubMed Link] | [ Full text ]
- Nair, P.; Tammariello, SP ; Estus, S. "Ceramide selectively inhibits apoptosis-associated events in NGF-deprived sympathetic neurons." Cell death and differentiation 7, 2 (2000): 207-14. [PubMed Link] | [ Full text ]
- Mukherjee, A.; Song, E.; Kihiko-Ehmann, M.; Goodman JP, Jr ; Pyrek, JS ; Estus, S.; Hersh, LB "Insulysin hydrolyzes amyloid beta peptides to products that are neither neurotoxic nor deposit on amyloid plaques." The Journal of neuroscience : the official journal of the Society for Neuroscience 20, 23 (2000): 8745-9. [PubMed Link] | [ Full text ]
- Aksenov, MY ; Tucker, HM ; Nair, P.; Aksenova, MV ; Butterfield, DA ; Estus, S.; Markesbery, WR "The expression of several mitochondrial and nuclear genes encoding the subunits of electron transport chain enzyme complexes, cytochrome c oxidase, and NADH dehydrogenase, in different brain regions in Alzheimer's disease." Neurochemical research 24, 6 (1999): 767-74. [PubMed Link] |
- Kihiko, ME ; Tucker, HM ; Rydel, RE ; Estus, S. "c-Jun contributes to amyloid beta-induced neuronal apoptosis but is not necessary for amyloid beta-induced c-jun induction." Journal of neurochemistry 73, 6 (1999): 2609-12. [PubMed Link] | [ Full text ]
- Chan, SL ; Tammariello, SP ; Estus, S.; Mattson, MP "Prostate apoptosis response-4 mediates trophic factor withdrawal-induced apoptosis of hippocampal neurons: actions prior to mitochondrial dysfunction and caspase activation." Journal of neurochemistry 73, 2 (1999): 502-12. [PubMed Link] | [ Full text ]
- Aksenov, MY ; Tucker, HM ; Nair, P.; Aksenova, MV ; Butterfield, DA ; Estus, S.; Markesbery, WR "The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease." Journal of molecular neuroscience : MN 11, 2 (1998): 151-64. [PubMed Link] | [ Full text ]
- Tucker, HM ; Rydel, RE ; Wright, S.; Estus, S. "Human amylin induces "apoptotic" pattern of gene expression concomitant with cortical neuronal apoptosis." Journal of neurochemistry 71, 2 (1998): 506-16. [PubMed Link] | [ Full text ]
- Estus, S.; Tucker, HM ; Rooyen, C.; Wright, S.; Brigham, EF ; Wogulis, M.; Rydel, RE "Aggregated amyloid-beta protein induces cortical neuronal apoptosis and concomitant "apoptotic" pattern of gene induction." The Journal of neuroscience : the official journal of the Society for Neuroscience 17, 20 (1997): 7736-45. [PubMed Link] | [ Full text ]
- Furukawa, K.; Estus, S.; Fu, W.; Mark, RJ ; Mattson, MP "Neuroprotective action of cycloheximide involves induction of bcl-2 and antioxidant pathways." The Journal of cell biology 136, 5 (1997): 1137-49. [PubMed Link] | [ Full text ]
- Freeman, RS ; Estus, S.; Johnson EM, Jr "Analysis of cell cycle-related gene expression in postmitotic neurons: selective induction of Cyclin D1 during programmed cell death." Neuron 12, 2 (1994): 343-55. [PubMed Link] | [ Full text ]
- Estus, S.; Zaks, WJ ; Freeman, RS ; Gruda, M.; Bravo, R.; Johnson EM, Jr "Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis." The Journal of cell biology 127, 6 Pt 1 (1994): 1717-27. [PubMed Link] | [ Full text ]
- Kotzbauer, PT ; Lampe, PA ; Estus, S.; Milbrandt, J.; Johnson EM, Jr "Postnatal development of survival responsiveness in rat sympathetic neurons to leukemia inhibitory factor and ciliary neurotrophic factor." Neuron 12, 4 (1994): 763-73. [PubMed Link] | [ Full text ]
- Freeman, RS ; Estus, S.; Horigome, K.; Johnson EM, Jr "Cell death genes in invertebrates and (maybe) vertebrates." Current opinion in neurobiology 3, 1 (1993): 25-31. [PubMed Link] |
- Shoji, M.; Golde, TE ; Ghiso, J.; Cheung, TT ; Estus, S.; Shaffer, LM ; Cai, XD ; McKay, DM ; Tintner, R.; Frangione, B. "Production of the Alzheimer amyloid beta protein by normal proteolytic processing." Science (New York, N.Y.) 258, 5079 (1992): 126-9. [PubMed Link] | [ Full text ]
- Golde, TE ; Estus, S.; Younkin, LH ; Selkoe, DJ ; Younkin, SG "Processing of the amyloid protein precursor to potentially amyloidogenic derivatives." Science (New York, N.Y.) 255, 5045 (1992): 728-30. [PubMed Link] | [ Full text ]
- Estus, S.; Golde, TE ; Kunishita, T.; Blades, D.; Lowery, D.; Eisen, M.; Usiak, M.; Qu, XM ; Tabira, T.; Greenberg, BD "Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor." Science (New York, N.Y.) 255, 5045 (1992): 726-8. [PubMed Link] | [ Full text ]
- Estus, S.; Golde, TE ; Younkin, SG "Normal processing of the Alzheimer's disease amyloid beta protein precursor generates potentially amyloidogenic carboxyl-terminal derivatives." Annals of the New York Academy of Sciences 674, (1992): 138-48. [PubMed Link] | [ Full text ]
- Golde, TE ; Estus, S.; Usiak, M.; Younkin, LH ; Younkin, SG "Expression of beta amyloid protein precursor mRNAs: recognition of a novel alternatively spliced form and quantitation in Alzheimer's disease using PCR." Neuron 4, 2 (1990): 253-67. [PubMed Link] | [ Full text ]
- Estus, S.; Blumer, JL "Critical period of phenytoin teratogenic action in the sea urchin, Arbacia punctulata embryo." The Journal of pharmacology and experimental therapeutics 251, 2 (1989): 782-9. [PubMed Link] | [ Full text ]
- Estus, S.; Blumer, JL "Role of microtubule assembly in phenytoin teratogenic action in the sea urchin (Arbacia punctulata) embryo." Molecular pharmacology 36, 5 (1989): 708-15. [PubMed Link] | [ Full text ]