FKBP52 in Neuronal Signaling and Neurodegenerative Diseases: A Microtubule Story

Abstract

The FK506-binding protein 52 (FKBP52) belongs to a large family of ubiquitously expressed and highly conserved proteins (FKBPs) that share an FKBP domain and possess Peptidyl-Prolyl Isomerase (PPIase) activity. PPIase activity catalyzes the isomerization of Peptidyl-Prolyl bonds and therefore influences target protein folding and function. FKBP52 is particularly abundant in the nervous system and is partially associated with the microtubule network in different cell types suggesting its implication in microtubule function. Various studies have focused on FKBP52, highlighting its importance in several neuronal microtubule-dependent signaling pathways and its possible implication in neurodegenerative diseases such as tauopathies (i.e., Alzheimer disease) and alpha-synucleinopathies (i.e., Parkinson disease). This review summarizes our current understanding of FKBP52 actions in the microtubule environment, its implication in neuronal signaling and function, its interactions with other members of the FKBPs family and its involvement in neurodegenerative disease.

Keywords: Alzheimer disease; FKBP52; Parkinson disease; Tau; microtubule; neurons; synuclein.

Figure 1

The three-dimensional structure of FKBP52 (aa1_459) showing the main structural domains. Functional domains are colored. The cartoon is generated with Pymol v0.99 and DOG 2.0. APP: amyloid precursor protein; FK: FK506 binding domain; Hsp90: heat shock protein of 90 kDa; SHR: steroid hormone receptor; TPR: tetratricopeptide repeat. References: (1) Chambraud et al, 1993; (2) Kamah et al, 2016; (3) Schreiber et al, 1991; (4) Harding et al, 1989; (5) Sanokawa-Akakura et al, 2010; (6) Silverstein et al, 1999; (7) Le Bihan et al, 1993; (8) Chambraud et al, 2007; (9) Tai et al, 1986; (10) Renoir et al, 1990; (11) Radanyi et al, 1994; (12) Massol et al, 1992.