Luigi Puglielli

Summary

Affiliation: University of Wisconsin
Country: USA

Publications

  1. ncbi request reprint Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease
    Cynthia M Carlsson
    Department of Medicine, Section of Geriatrics and Gerontology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
    J Alzheimers Dis 13:187-97. 2008
  2. pmc Aging of the brain, neurotrophin signaling, and Alzheimer's disease: is IGF1-R the common culprit?
    Luigi Puglielli
    Department of Medicine, University of Wisconsin Madison, and Geriatric Research Education Clinical Center, VA Medical Center, VAH GRECC 11G, 2500 Overlook Terrace, Madison, WI 53705, USA
    Neurobiol Aging 29:795-811. 2008
  3. pmc Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature death
    Mariana Pehar
    Department of Medicine, University of Wisconsin Madison, WI 53705, USA
    Aging Cell 9:174-90. 2010
  4. pmc Biochemical inhibition of the acetyltransferases ATase1 and ATase2 reduces β-secretase (BACE1) levels and Aβ generation
    Yun Ding
    Department of Medicine, University of Wisconsin Madison, Madison, Wisconsin 53705, USA
    J Biol Chem 287:8424-33. 2012
  5. pmc Egr-1 and Hipk2 are required for the TrkA to p75(NTR) switch that occurs downstream of IGF1-R
    Hui Li
    Department of Medicine, University of Wisconsin Madison, Madison, WI 53705, USA
    Neurobiol Aging 30:2010-20. 2009
  6. pmc Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels
    Mi Hee Ko
    Department of Medicine, University of Wisconsin Madison and Geriatric Research Education Clinical Center, Veterans Affairs Medical Center, Madison, Wisconsin 53705, USA
    J Biol Chem 284:2482-92. 2009
  7. pmc SLC33A1/AT-1 protein regulates the induction of autophagy downstream of IRE1/XBP1 pathway
    Mariana Pehar
    Department of Medicine, University of Wisconsin, Madison, WI 53705, USA
    J Biol Chem 287:29921-30. 2012
  8. pmc PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1
    Mary Cabell Jonas
    Department of Medicine, University of Wisconsin Madison, VAH GRECC 11G, 2500 Overlook Terrace, Madison, Wisconsin 53705, USA
    EMBO Rep 9:916-22. 2008
  9. pmc An aging pathway controls the TrkA to p75NTR receptor switch and amyloid beta-peptide generation
    Claudio Costantini
    Department of Medicine, University of Wisconsin Madison, Veterans Administration Hospital GRECC 11G, 53705, USA
    EMBO J 25:1997-2006. 2006
  10. pmc AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability
    Mary Cabell Jonas
    Department of Medicine, University of Wisconsin Madison, Madison, WI 53705, USA
    J Cell Sci 123:3378-88. 2010

Research Grants

  1. Second messenger ceramide in Alzheimer's disease
    Luigi Puglielli; Fiscal Year: 2004
  2. Second messenger ceramide in Alzheimer's disease
    Luigi Puglielli; Fiscal Year: 2006
  3. Second messenger ceramide in Alzheimer's disease
    Luigi Puglielli; Fiscal Year: 2007
  4. Aging and Alzheimer's Disease Potential Link with IGF1-R
    Luigi Puglielli; Fiscal Year: 2009
  5. Aging and Alzheimer's Disease Potential Link with IGF1-R
    Luigi Puglielli; Fiscal Year: 2010
  6. Second messenger ceramide in Alzheimer's disease
    Luigi Puglielli; Fiscal Year: 2005

Collaborators

Detail Information

Publications22

  1. ncbi request reprint Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease
    Cynthia M Carlsson
    Department of Medicine, Section of Geriatrics and Gerontology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA
    J Alzheimers Dis 13:187-97. 2008
    ..It is unclear if statins modify Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD...
  2. pmc Aging of the brain, neurotrophin signaling, and Alzheimer's disease: is IGF1-R the common culprit?
    Luigi Puglielli
    Department of Medicine, University of Wisconsin Madison, and Geriatric Research Education Clinical Center, VA Medical Center, VAH GRECC 11G, 2500 Overlook Terrace, Madison, WI 53705, USA
    Neurobiol Aging 29:795-811. 2008
    ..Future research will determine how far the connection goes and how much of it we can influence...
  3. pmc Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature death
    Mariana Pehar
    Department of Medicine, University of Wisconsin Madison, WI 53705, USA
    Aging Cell 9:174-90. 2010
    ..Importantly, Igf1r haploinsufficiency was also able to correct the synaptic deficits of APP(695/swe) mice, a model of Alzheimer's disease...
  4. pmc Biochemical inhibition of the acetyltransferases ATase1 and ATase2 reduces β-secretase (BACE1) levels and Aβ generation
    Yun Ding
    Department of Medicine, University of Wisconsin Madison, Madison, Wisconsin 53705, USA
    J Biol Chem 287:8424-33. 2012
    ..The mechanism of action involves competitive and non-competitive inhibition as well as generation of unstable intermediates of the ATases that undergo degradation...
  5. pmc Egr-1 and Hipk2 are required for the TrkA to p75(NTR) switch that occurs downstream of IGF1-R
    Hui Li
    Department of Medicine, University of Wisconsin Madison, Madison, WI 53705, USA
    Neurobiol Aging 30:2010-20. 2009
    ..Such an event is opposed by caloric restriction, a model of delayed aging, and favored by the p44 transgene in p44(+/+) animals, a model of accelerated aging...
  6. pmc Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels
    Mi Hee Ko
    Department of Medicine, University of Wisconsin Madison and Geriatric Research Education Clinical Center, Veterans Affairs Medical Center, Madison, Wisconsin 53705, USA
    J Biol Chem 284:2482-92. 2009
    ..The biochemical characterization of the above events could lead to the identification of novel pharmacological strategies for the prevention of this form of dementia...
  7. pmc SLC33A1/AT-1 protein regulates the induction of autophagy downstream of IRE1/XBP1 pathway
    Mariana Pehar
    Department of Medicine, University of Wisconsin, Madison, WI 53705, USA
    J Biol Chem 287:29921-30. 2012
    ..Failure to induce AT-1 leads to widespread autophagic cell death. Mechanistically, the regulation of the autophagic process involves N(ε)-lysine acetylation of Atg9A...
  8. pmc PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1
    Mary Cabell Jonas
    Department of Medicine, University of Wisconsin Madison, VAH GRECC 11G, 2500 Overlook Terrace, Madison, Wisconsin 53705, USA
    EMBO Rep 9:916-22. 2008
    ..In addition, Pcsk9(-/-) mice showed increased levels of BACE1 and Abeta in the brain. Finally, we found that nascent low-density lipoprotein receptor, a known substrate of PCSK9, is also acetylated...
  9. pmc An aging pathway controls the TrkA to p75NTR receptor switch and amyloid beta-peptide generation
    Claudio Costantini
    Department of Medicine, University of Wisconsin Madison, Veterans Administration Hospital GRECC 11G, 53705, USA
    EMBO J 25:1997-2006. 2006
    ..We also show that hyperactivation of IGF1-R signaling in p44 transgenic animals, which show an accelerated form of aging, is characterized by early TrkA-to-p75(NTR) switch and increased production of Abeta in the brain...
  10. pmc AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability
    Mary Cabell Jonas
    Department of Medicine, University of Wisconsin Madison, Madison, WI 53705, USA
    J Cell Sci 123:3378-88. 2010
    ..Finally, we show that AT-1 is essential for cell viability as its downregulation results in widespread cell death and induction of features characteristic of autophagy...
  11. pmc A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1
    Claudio Costantini
    Department of Medicine, University of Madison Wisconsin, Madison, WI 53705, USA
    Biochem J 407:383-95. 2007
    ..Site-directed mutagenesis indicates that lysine acetylation is necessary for nascent BACE1 to leave the ER and move ahead in the secretory pathway, and for the molecular stabilization of the protein...
  12. ncbi request reprint The sterol carrier protein SCP-x/pro-SCP-2 gene has transcriptional activity and regulates the Alzheimer disease gamma-secretase
    Mi Hee Ko
    Department of Medicine, University of Wisconsin Madison, Madison, Wisconsin 53705, USA
    J Biol Chem 282:19742-52. 2007
    ..In conclusion, we have identified two novel functions (transcriptional and transcription regulatory) of the SCP-x/pro-SCP-2 gene that have impact on gamma-secretase activity...
  13. pmc Lysine acetylation in the lumen of the ER: a novel and essential function under the control of the UPR
    Mariana Pehar
    Department of Medicine, University of Wisconsin Madison, VA Medical Center, Madison, WI 53705, USA
    Biochim Biophys Acta 1833:686-97. 2013
    ..Here, we describe these exciting findings as well as recent biochemical and cellular advances, and discuss possible impact on both human physiology and pathology...
  14. pmc Proteomic assessment shows that many endoplasmic reticulum (ER)-resident proteins are targeted by N(epsilon)-lysine acetylation in the lumen of the organelle and predicts broad biological impact
    Mariana Pehar
    Department of Medicine, University of Wisconsin, Madison, Wisconsin 53705, USA
    J Biol Chem 287:22436-40. 2012
    ..As such, it is predicted to play a fundamental role in human physiology as well as human pathology...
  15. pmc P44, the 'longevity-assurance' isoform of P53, regulates tau phosphorylation and is activated in an age-dependent fashion
    Mariana Pehar
    Department of Medicine, University of Wisconsin Madison, 2500 Overlook Terrace, Madison, WI, 53705, USA
    Aging Cell 13:449-56. 2014
    ..Taken together, these results suggest that an imbalance in the p53:p44 ratio might be involved with the altered tau metabolism that characterizes aging...
  16. pmc Calorie restriction attenuates astrogliosis but not amyloid plaque load in aged rhesus macaques: a preliminary quantitative imaging study
    Aadhavi Sridharan
    Medical Scientist Training Program, University of Wisconsin Madison, 750 Highland Ave, Madison, WI 53705, USA
    Brain Res 1508:1-8. 2013
    ..The present study is a preliminary post-mortem histological analysis of the effects of CR on brain health, and further studies using molecular and biochemical techniques are warranted to elucidate underlying mechanisms...
  17. pmc A TrkA-to-p75NTR molecular switch activates amyloid beta-peptide generation during aging
    Claudio Costantini
    Department of Medicine, University of Wisconsin Madison, Wm S Middleton Memorial Veteran s Hospital, Madison, WI 53705, USA
    Biochem J 391:59-67. 2005
    ....
  18. ncbi request reprint Alzheimer's disease: the cholesterol connection
    Luigi Puglielli
    Neurobiology of Disease Laboratory, CAGN, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Nat Neurosci 6:345-51. 2003
    ..In this review, we describe recent findings concerning the molecular mechanisms underlying the cholesterol-AD connection...
  19. pmc Alzheimer disease beta-amyloid activity mimics cholesterol oxidase
    Luigi Puglielli
    Neurobiology of Disease Laboratory, Genetics and Aging Research Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA
    J Clin Invest 115:2556-63. 2005
    ..Cu2+-mediated oxidation of cholesterol may be a pathogenic mechanism common to atherosclerosis and AD...
  20. ncbi request reprint The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease
    Birgit Hutter-Paier
    JSW Research Forschungslabor GmbH, Institute of Experimental Pharmacology, Rankengasse 28, 8020 Graz, Austria
    Neuron 44:227-38. 2004
    ..Our results suggest that ACAT inhibition may be effective in the prevention and treatment of AD by inhibiting generation of the Abeta peptide...
  21. ncbi request reprint Role of acyl-coenzyme a: cholesterol acyltransferase activity in the processing of the amyloid precursor protein
    Luigi Puglielli
    Neurobiology of Disease Laboratory, Genetics and Aging Research Unit NIND, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Mol Neurosci 24:93-6. 2004
    ..Future mechanistic and transgenic animal studies are needed to evaluate the potential use of ACAT inhibitors in the therapeutic treatment or prevention of AD...
  22. ncbi request reprint Ceramide stabilizes beta-site amyloid precursor protein-cleaving enzyme 1 and promotes amyloid beta-peptide biogenesis
    Luigi Puglielli
    Neurobiology of Disease Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA
    J Biol Chem 278:19777-83. 2003
    ..Taken together, these data indicate that the lipid second messenger ceramide, which is elevated in the brains of Alzheimer's disease patients, increases the half-life of BACE1 and thereby promotes Abeta biogenesis...

Research Grants7

  1. Second messenger ceramide in Alzheimer's disease
    Luigi Puglielli; Fiscal Year: 2004
    ..nSMase activity and ceramide levels will be analyzed in both aging neurons and organotypic brain cultures. The effects of nSMase inhibitors in AD pathology will be analyzed using "AD transgenic mice". ..
  2. Second messenger ceramide in Alzheimer's disease
    Luigi Puglielli; Fiscal Year: 2006
    ..nSMase activity and ceramide levels will be analyzed in both aging neurons and organotypic brain cultures. The effects of nSMase inhibitors in AD pathology will be analyzed using "AD transgenic mice". ..
  3. Second messenger ceramide in Alzheimer's disease
    Luigi Puglielli; Fiscal Year: 2007
    ..nSMase activity and ceramide levels will be analyzed in both aging neurons and organotypic brain cultures. The effects of nSMase inhibitors in AD pathology will be analyzed using "AD transgenic mice". ..
  4. Aging and Alzheimer's Disease Potential Link with IGF1-R
    Luigi Puglielli; Fiscal Year: 2009
    ..The long-term objective of this proposal is to expand upon our findings and fully characterize the molecular pathway that we have identified. This will allow us to design new pharmacologic approaches for the prevention of AD. ..
  5. Aging and Alzheimer's Disease Potential Link with IGF1-R
    Luigi Puglielli; Fiscal Year: 2010
    ..The long-term objective of this proposal is to expand upon our findings and fully characterize the molecular pathway that we have identified. This will allow us to design new pharmacologic approaches for the prevention of AD. ..
  6. Second messenger ceramide in Alzheimer's disease
    Luigi Puglielli; Fiscal Year: 2005
    ..nSMase activity and ceramide levels will be analyzed in both aging neurons and organotypic brain cultures. The effects of nSMase inhibitors in AD pathology will be analyzed using "AD transgenic mice". ..