Stabilization of alpha-synuclein protein with aging and familial parkinson's disease-linked A53T mutation - PubMed (original) (raw)

α-Syn expression during human brain aging. A, Representative autoradiogram of RT-PCR-amplified mRNAs encodingα-Syn,β-Syn,γ-Syn, and GAPDH (GD). The cDNAs were derived from human Fcx, Caud, and SN. Representative results from three examples (19-, 53-, and 80-year-old neurologically normal human subjects) from six subjects are shown. Each sample was analyzed in triplicate and presented graphically in C. B, Immunoblot analysis of human Fcx, Caud, and SN extracts of Syn. Brain extracts from human subjects in their 50s and 80-90s were examined. The results from younger subjects are shown in supplemental Figure S2 (available at

www.jneurosci.org/cgi/content/full/24/33/9400/DC1

). C, The levels of mRNAs encoding α-Syn, β-Syn, and γ-Syn in Fcx, Caud, and SN were quantified from the RT-PCR analysis shown in A. The scatter plot and the calculated regression lines show that the levels of mRNAs encoding α-Syn decrease with aging in all brain regions, whereas the expression of mRNA encoding γ-Syn remains constant. The pattern of β-Syn expression is more variable. _R_2 and p values are as follows (asterisks indicate statistically significant p values): α-Syn [Fcx (0.628, 0.0021*), Caud (0.393, 0.0291*), SN (0.03026, 0.0639)]; β-Syn [Fcx (0.5506, 0.014*), Caud and SN (<0.1, >0.5)]; γ-Syn [all (<0.1, >0.3)]. D, The levels of Syn polypeptides in brain regions were quantified from the immunoblots shown in B. For each subject, the analysis was performed in duplicate, and the levels of Syn isotypes were normalized to GAPDH. The subjects were grouped as 50s (49-58 years old) and 80+ (83-95 years old) and are shown as mean and SEM. To facilitate presentation of all three Syn isotypes, values are plotted as the percents average of the subjects in their 50s. The average relative levels show that the levels of α-Syn in SN almost double during this 30 year span (**p < 0.01; t test). Although the α-Syn protein levels in Fcx do not change between 50s and 80+, an analysis of younger subjects shows an increase at younger ages (supplemental Fig. S2, available at

www.jneurosci.org/cgi/content/full/24/33/9400/DC1

). The decease in the cortical γ-level is significant (*p < 0.05) only when GAPDH is used as the reference protein.