Luigi Puglielli

Position title: Professor, Department of Medicine


Phone: (608) 280-7000

Luigi Puglielli headshot


M.D., Ph.D. Catholic University of Rome (Italy)

Research Focus:

The Molecular Mechanisms Responsible for the Cognitive Decline That Accompanies Aging, and the Molecular Pathogenesis of Neurodegenerative Diseases

Research Description:

Our research uses multidisciplinary approaches on in vitro, ex vivo, and in vivo models.  Such approaches include biochemical, cellular, and molecular techniques, as well as electrophysiological, cognitive/behavioral, and structural analysis.

Active projects include:

  1. Molecular mechanisms of cognitive loss during aging and Alzheimer’s disease neuropathology. We have identified a novel link between aging and Alzheimer’s disease, which, when hyperactive, results in synaptic and cognitive deficits, and in severe degeneration of memory-forming and -retrieving areas of the brain. The molecular mechanisms involved in these events are being actively sought.
  2. The ER acetylation machinery.  In 2007, we reported that nascent membrane proteins undergo transient lysine acetylation in the lumen of the endoplasmic reticulum (ER).  Since then we have idenified the entire ER acetylation machinery and shown that it plays an essential role in the basic biology of the cell.  This machinery impacts on different neurodevelopmental and neurodegenerative disease (such as familial spastic paraplegia, autism spectrum disorder and mental retardation, and Alzheimer’s disease) as well as propensity to infections and cancer.  New relevant animal models are being generated to extend our findings.
  3. Drug discovery for the prevention of Alzheimer’s disease. We have identified compounds that block some of the early biochemical events involved in the pathogenesis of Alzheimer’s disease. They target the ER-based lysine acetylation machinery identified in our laboratory. Mechanisms of action as well as therapeutic potential are being actively studied.

Link to Publications