Fig. 3

mTORC1 pathway and regulatory protein changes in human brain. Relative levels of phosphorylated forms and activity status of several major mTOR pathway components and regulators (PTEN, mTORC2, REDD1, AMPK) in neurodegenerative disorders. Only those studies that examined human AD/DS (Alzheimer's, Down's Syndrome), PD (Parkinson's), HD (Huntington's) or ALS (Amyotrophic Lateral Sclerosis) brain or peripheral cells (WBCs) are listed. In addition to those studies cited in Table 1, that examined mTOR pathway proper, we include those here that did not but still focus on one or more of the other components. In so far as the number of studies supporting a given direction of change (references reporting decreased levels in blue, increased in red, in affected vs. control brain) can be taken as some measure of consensus, each publication listed is represented visually by a single red (increased) or blue (decreased) dot next to the respective pathway protein. The dot also indicates the corresponding disease. Most studies only examined basal phospho-levels, whereas a few specified insulin-induced activations or assayed the enzymatic activity. For example, the majority of studies in AD brain favor basal mTORC1 over-activation (vs. inhibition; n=11 vs. 5); increased IRS-1 phospho-inhibition (5); AMPK over-activation (4) and increased 4EBP1 phospho-inhibition (5 vs. 2), whereas a more modest majority, favors Akt over-activation (8 vs. 5) and p-p70S6K hyperactivation (7 vs. 5). Nevertheless, the Akt and mTOR activation responses to insulin are depressed in cell model [135] and AD brain [136]