Research Paper Volume 12, Issue 20 pp 20702—20727

Stress-induced p53 drives BAG5 cochaperone expression to control α-synuclein aggregation in Parkinson's disease

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BAG5 is increased and colocalized with α-synuclein in SNCA p.A53T mice and PD patients. (A) Immunohistochemical staining of substantia nigra sections with a phospho-α-synuclein (Ser129) antibody revealed that the phospho-α-synuclein (Ser129) is expressed mainly in the substantia nigra. The expression of BAG5 (red) and p-α-synuclein (green) was detected mainly at the TH (blue)-positive excitatory synapse in SNCA p.A53T mice. The bars indicate 20 μm (Student’s t-test; **, p < 0.01). (B) Lysates were prepared from human normal control and PD brains. Immunoprecipitations were performed with an anti-BAG5 antibody. Immunoprecipitates were sequentially probed with phospho-α-synuclein (Ser129), anti-α-synuclein, and anti-HSP70 antibodies. Five percent of each lysate used for immunoprecipitation was loaded as input and probed with anti-BAG5, phospho-α-synuclein (Ser129), anti- α-synuclein, and anti-HSP70 antibodies. β-Actin was used as a loading control.