title: Role of the microtubule-associated TPPP/p25 in Parkinson's and related diseases and its therapeutic potential.
abstract: The discovery and development of therapeutic strategies for the treatments of Parkinson's disease (PD) and other synucleinopathies are limited by a lack of understanding of the pathomechanisms and their connection with different diseases such as cancers. Areas covered: The hallmarks of these diseases are frequently multifunctional disordered proteins displaying moonlighting and/or chameleon features, which are challenging drug targets. A representative of these proteins is the disordered Tubulin Polymerization Promoting Protein (TPPP/p25) expressed specifically in oligodendrocytes (OLGs) in normal brain. Its non-physiological level is tightly related to the etiology of PD and Multiple System Atrophy (TPPP/p25 enrichment in inclusions of neurons and OLGs, respectively), multiple sclerosis (TPPP/p25-positive OLG destruction), as well as glioma (loss of TPPP/p25 expression). The established anti-proliferative potency of TPPP/p25 may raise its influence in cancer development. The recognition that whereas too much TPPP/p25 could kill neurons in PD, but its loss keeps cells alive in cancer could contribute to our understanding of the interrelationship of 'TPPP/p25 diseases'. Expert commentary: The knowledge accumulated so far underlines the key roles of the multifunctional TPPP/p25 in both physiological and diverse pathological processes, consequently its validation as drug target sorely needs a new innovative strategy that is briefly reviewed here.
authors.affiliation: a Institute of Enzymology , Research Centre for Natural Sciences, Hungarian Academy of Sciences , Budapest , Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Oláh
authors.affiliation: b Institute of Chemistry for Materials and Medias, UMR CNRS 7285, University of Poitiers, 4 Rue Michel Brunet , TSA 51106 Poitiers cedex 9, France.|c REpiCGO network, Cancéropôle Grand Ouest, Maison de la Recherche en Santé, 63, quai Magellan 44000 Nantes , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
authors.affiliation: a Institute of Enzymology , Research Centre for Natural Sciences, Hungarian Academy of Sciences , Budapest , Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Ovádi
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D005786:Gene Expression Regulation; D005910:Glioma / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics / Q000503:physiopathology; D019578:Multiple System Atrophy / Q000235:genetics / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology
chemical_list: D009419:Nerve Tissue Proteins; C118136:TPPP protein, human
keywords: CNS diseases; cancer; drug target; microtubule; protein chameleon; tubulin deacetylases; tubulin polymerization promoting protein/p25; validation; α-synuclein