Interactions of pathological hallmark proteins: Tubulin polymerization promoting protein/p25, {beta}-amyloid and {alpha}-synuclein

The disordered tubulin polymerization promoting protein (TPPP/p25) was found to be co-enriched in neuronal and glial inclusions with α-synuclein in Parkinson disease and multiple system atrophy, respectively; however, co-occurrence of α-synuclein with β-amyloid (Aβ) in human brain inclusions has been recently reported, suggesting the existence of mixed type pathologies that could result in obstacles in the correct diagnosis and treatment. Here we identified TPPP/p25 as an interacting partner of the soluble Aβ oligomers as major risk factors for Alzheimer disease using ProtoArray human protein microarray. The interactions of oligomeric Aβ with proteins involved in the etiology of neurological disorders were characterized by ELISA, surface plasmon resonance, pelleting experiments, and tubulin polymerization assay. We showed that the Aβ(42) tightly bound to TPPP/p25 (K(d) = 85 nm) and caused aberrant protein aggregation by inhibiting the physiologically relevant TPPP/p25-derived microtubule assembly. The pair-wise interactions of Aβ(42), α-synuclein, and tubulin were found to be relatively weak; however, these three components formed soluble ternary complex exclusively in the absence of TPPP/p25. The aggregation-facilitating activity of TPPP/p25 and its interaction with Aβ was monitored by electron microscopy with purified proteins by pelleting experiments with cell-free extracts as well as by confocal microscopy with CHO cells expressing TPPP/p25 or amyloid. The finding that the interaction of TPPP/p25 with Aβ can produce pathological-like aggregates is tightly coupled with unusual pathology of the Alzheimer disease revealed previously; that is, partial co-localization of Aβ and TPPP/p25 in the case of diffuse Lewy body disease with Alzheimer disease

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Low temperature delay and inhibition of a plant defence mechanism: early basal resistance in tobacco

The development of local early basal resistance (EBR), is a form of non-specific general defence response of plants to bacteria, greatly depending on temperature. This symptomless defence mechanism is easily detected by its inhibitory action on the hypersensitive response (HR) caused by a subsequent incompatible pathogenic bacterium. Both EBR and HR were investigated at different temperatures ranging from 30 °C to 5 °C. At normal temperatures (30-20 °C) both heat-killed Pseudomonas syringae pv. syringae 61 (polyvirulent to many plants) and Pseudomonas savastanoi pv. phaseolicola S21 (pathogenic to bean) induced EBR in tobacco leaves within a few hours, but below 10 °C it was greatly delayed and at 5 °C usually no EBR response could be detected within 2-3 days. The time required for development of EBR did not depend on the bacterial pathovars or strains. However, the induction time of HR was not as sensitive to low temperatures as that of EBR, instead, it depended on the bacterial pathovars used