Title:Alzheimer’s Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy
Volume: 22
Issue: 26
Author(s): Antonella Marino Gammazza, Celeste Caruso Bavisotto, Rosario Barone, Everly Conway de Macario and Alberto J.L. Macario
Affiliation:
Keywords:
Chaperonopathies, protein-misfolding diseases, Alzheimer’s disease, β-amyloid, tau, molecular chaperones, chaperonotherapy.
Abstract: Background: Alzheimer’s disease (AD) is a dementia, a neurodegenerative condition,
and a protein-misfolding disease or proteinopathy, characterized by protein deposits,
extracellular plaques and intracellular neurofibrillary tangles, which contain the AD’s typical
pathological proteins, abnormal β-amyloid and hyperphosphorylated tau, respectively,
and are located predominantly in the cortex of the frontal, parietal, and temporal brain
lobes. What is the role of molecular chaperones in AD? Data indicate that molecular
chaperones, also known as Hsp, are involved in AD, probably displaying protective roles
and/or acting as pathogenic factors as it occurs in chaperonopathies in which case AD
would be suitable to chaperonotherapy. Hsp60, Hsp70, and Hsp90 can be augmented and
overexpressed or diminished and downregulated in various situations in AD affected tissues
and cells, indicating they are active during disease development and progression.
Question: What is the role of molecular chaperones in AD? Data indicate that molecular
chaperones, also known as Hsp, are involved in AD, probably displaying protective roles and/or acting as
pathogenic factors as it occurs in chaperonopathies in which case AD would be suitable to chaperonotherapy.
Objective: Investigate the role of Hsp in AD, focusing on Hsp60, Hsp70, and Hsp90. Method: Critical
examination of published data. Results: Hsp60, Hsp70, and Hsp90 can be augmented and overexpressed or
diminished and downregulated in various situations in AD affected tissues and cells, indicating they are active
during disease development and progression. Conclusion and Perspectives: Notwithstanding that the roles and
mechanisms of action of chaperones in AD are still incompletely understood, there is already enough evidence
to encourage the development of therapeutic strategies targeting them, either to block their activity in case they
promote disease progression or to boost their performance when they are protective. The latter is an example of
positive chaperonotherapy, which also includes chaperone replacement via gene or protein administration. On
the contrary, if a chaperone is found to help the disease, it has to be blocked or eliminated, which constitute
modalities of negative chaperonotherapy.
