Natively unfolded tubulin polymerization promoting protein TPPP/p25 is a common marker of alpha-synucleinopathies.
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.
Institute of Neurology, Medical University of Vienna, A-1097 Vienna, Austria.
Gábor G
GG
Kovács
Lajos
L
László
János
J
Kovács
Poul Henning
PH
Jensen
Evo
E
Lindersson
Gergo
G
Botond
Tamás
T
Molnár
András
A
Perczel
Ferenc
F
Hudecz
Gábor
G
Mezo
Anna
A
Erdei
László
L
Tirián
Attila
A
Lehotzky
Ellen
E
Gelpi
Herbert
H
Budka
Judit
J
Ovádi
D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D005260:Female; D006801:Humans; D007106:Immune Sera; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D017510:Protein Folding; D051843:Synucleins; D051844:alpha-Synuclein
D015415:Biomarkers; D007106:Immune Sera; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; C118136:TPPP protein, human; D051844:alpha-Synuclein