Natively unfolded tubulin polymerization promoting protein TPPP/p25 is a common marker of alpha-synucleinopathies

• Main Authors: Gábor G. Kovács, Lajos László, János Kovács, Poul Henning Jensen, Evo Lindersson, Gergő Botond, Tamás Molnár, András Perczel, Ferenc Hudecz, Gábor Mező, Anna Erdei, László Tirián, Attila Lehotzky, Ellen Gelpi, Herbert Budka, Judit Ovádi
• Format: Article
• Language: English
• Published: Elsevier 2004-11-01
• Series: Neurobiology of Disease
• Subjects: TPPP/p25; Microtubule; Alpha-synuclein; Tau; Parkinson's disease; Alzheimer's disease
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996104001366

The novel basic, heat-stable tubulin polymerization promoting protein TPPP/p25 is associated with microtubules in vitro and can induce the formation of aberrant microtubule assemblies. We show by 1H-NMR spectroscopy that TPPP/p25 is natively unfolded. Antisera against peptide 186GKGKAGRVDLVDESG200NH2 (186–200) are highly specific to TPPP/p25. Immunohistochemistry and confocal microscopy demonstrates that TPPP/p25 is enriched in filamentous alpha-synuclein bearing Lewy bodies of Parkinson's (PD) and diffuse Lewy body disease (DLBD), as well as glial inclusions of multiple system atrophy (MSA). There is a correlation between TPPP/p25 and alpha-synuclein immunoreactivity in Western blot. In contrast, TPPP/p25 is not associated with abnormally phosphorylated tau in various inclusions of Pick's disease (PiD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). However, electron microscopy confirms clusters of TPPP/p25 immunoreactivity along filaments of unstructured but not compact neurofibrillary tangles in Alzheimer's disease (AD). TPPP/p25 seems to be a novel marker of alpha-synucleinopathies.