Defects of energy metabolism contributes to neurodegeneration
Universita degli Studi di Roma 'La Sapienza'
Dep of Biochemical Sciences, Sapienza University of Rome P.le aldo moro 5, 00185 Rome (IT)
Marzia perluigi, eugenio barone, fabio di domenico
Marzia perluigi, eugenio barone, fabio di domenico
English, Italian
4 weeks
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
Yes Yes Yes No No No No No Yes Yes No No
Type of Research Project
- Basic science
What is the background of the project?
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder and represents one of the most disabling conditions. AD shares many features in common with systemic insulin resistance diseases, suggesting that it can be considered as a metabolic disease, characterized by reduced insulin-stimulated growth and survival signaling, increased oxidative stress (OS), proinflammatory cytokine activation, mitochondrial dysfunction, impaired energy metabolism, and altered protein homeostasis. Reduced glucose utilization and energy metabolism in AD have been associated with the buildup of amyloid-β peptide and hyperphosphorylated tau, increased OS, and the accumulation of unfolded/misfolded proteins. Mammalian target of rapamycin (mTOR), which is aberrantly activated in AD since early stages, plays a key role during AD neurodegeneration by, on one side, inhibiting insulin signaling as a negative feedback mechanism and, on the other side, regulating protein homeostasis. It is likely that the concomitant and mutual alterations of energy metabolism-mTOR signaling-protein homeostasis might represent a self-sustaining triangle of harmful events that trigger the degeneration and death of neurons and the development and progression of AD.
What is the aim of the project?
This project aims to understand the role of metabolic dysfuntion, both systemic and central, that contribute to loss of enuronal function ultimately leading to the development of alzheimer disease.
What techniques and methods are used?
To unravel the key metbolic defects that affect neuronal homeostasi, we will focus on insulin signalinng and downstream targets by using proteomics, western blot, immunofluorescence, rpimary and immortalized cell cultures. In addition RT-PCR (reverse transcriptase-polymerase chain reaction) and cell trafsection will be performed to better understand the role of specific genes.
What is the role of the student?
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will be trained to learn how: Collect samples (cells, tissue or plasma) Prepare sample solutions according to the experimenatl plan Measure protein or DNA content Learn basic data analysis Become independent to execute an experimental protocol, though with assistance of post-docs Identify failure/problem of experiments when occuring and learn basic problem solving approaches
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
No. Some preliminry readings and trainign by post-doc in my lab. Studnets will be daily supervised
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Ability to work in a team. Subjects passed: biochemistry
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts:
- Medical students
- Graduated students (less than 6 months)
- Pre-Medical students from the American-British system
- 1) Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. Chen Z Prog Neurobiol 2013 108:21-43
- 2) Oxidative stress; dysfunctional glucose metabolism and Alzheimer disease. Butterfield DA; Halliwell B. Nat Rev Neurosci. 2019;20(3):148-160