Affiliations: [a] Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0305, USA | [b] Graduate Center for Gerontology, University of Kentucky, Lexington, KY 40536-0305, USA | [c] Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536-0305, USA | [d] Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY 40536-0305, USA
Correspondence:
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Corresponding author: James W. Geddes, Ph.D., 228 Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0305, USA. Tel.: 859 257 1412 ext. 254; Fax: 859 323 2866; E-mail: jgeddes@uky.edu.
Abstract: Impaired tau catabolism may contribute to tau accumulation and aggregation in Alzheimer's disease and neurofibrillary tangle formation. This study examined the effects of proteasome and calpain inhibition on tau levels and turnover in primary rat hippocampal neurons and differentiated SH-SY5Y human neuroblastoma cells. Administration of proteasome (MG-115, lactacystin) or calpain (MDL28170) inhibitors for up to 24 hours did not alter tau levels in differentiated SH-SY5Y cells or rat hippocampal neurons. Addition of 1 μM and 10 μM MG-115 did not change total tau levels, but did result in increased reactivity of phosphorylation-dependent tau antibodies (PHF-1, CP-13) and decreased Tau-1 immunoreactivity. Administration of cycloheximide to inhibit de novo protein synthesis also did not alter tau levels in the presence or absence of lactacystin. These results demonstrate that although the proteasome and calpain protease systems are capable of degrading tau in cell-free assays, their inhibition does not alter cellular tau levels in primary neurons or differentiated neuroblastoma cells.
