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Pavel Pavlov

Molecular chaperone network and neurodegeneration

Research focus

Development of novel modulators of molecular chaperone network with focus on Alzheimer disease therapy

Most of the neurodegenerative diseases can be classified as proteinopathies or protein misfolding disorders with intra- or extracellular aggregation of certain proteins or peptides observed in affected brain areas. Molecular chaperones are primarily responsible for maintenance of intracellular protein homeostasis including protein folding, transport and degradation. Molecular chaperones as masters of protein homeostasis can be an attractive pharmacological target. However, assuming a long-term therapy for neurodegenerative diseases, the general inhibition or activation of molecular chaperone function can be detrimental. However, we can regulate specific cellular processes avoiding generalized effect on molecular chaperone system by inhibition of protein-protein interactions between molecular chaperones and their particular partner co-chaperones.

Specific goals of the project are following:

1. Develop potent and specific lead compounds inhibiting particular chaperone-co-chaperone interactions.

2. Generate proof-of-concept biological data supporting our drug development program.

Group members

Anknuten

Pavel Pavlov

Enhet: Winblad
E-post: pavel.pavlov@ki.se

Postdoc

Rajnish Kumar

Enhet: Institutionen för Neurobiologi, Vårdvetenskap och Samhälle (NVS), H1
E-post: rajnish.kumar@ki.se

Selected publications

Combined x-ray crystallography and computational modeling approach to investigate the Hsp90 C-terminal peptide binding to FKBP51.
Kumar R, Moche M, Winblad B, Pavlov P
Sci Rep 2017 Oct;7(1):14288

Development of GMP-1 a molecular chaperone network modulator protecting mitochondrial function and its assessment in fly and mice models of Alzheimer's disease.
Pavlov P, Hutter-Paier B, Havas D, Windisch M, Winblad B
J. Cell. Mol. Med. 2018 Jul;22(7):3464-3474