Abstract
Berberine is a primary component of the most functional extracts of Coptidis rhizome used in traditional Chinese medicine for centuries. Recent reports indicate that Berberine has the potential to prevent and treat Alzheimer's disease (AD). The previous studies reported that Calyculin A (CA) impaired the axonal transport in neuroblastoma-2a (N2a) cells. Berberine attenuated tau hyperphosphorylation and cytotoxicity induced by CA. Our study aimed at investigating the effects of Berberine on the axonal transport impairment induced by CA in N2a cells. The results showed that Berberine could protect the cell from CA -induced toxicity in metabolism and viability, as well as hyperphosphorylation of tau and neurofilaments (NFs). Furthermore, Berberine could reverse CA-induced axonal transport impairment significantly. Berberine also partially reversed the phosphorylation of the catalytic subunit of PP-2A at Tyrosine 307, a crucial site negatively regulating the activity of PP-2A, and reduced the levels of malondialdehyde and the activity of superoxide dismutase, markers of oxidative stress, induced by CA. The present work for the first time demonstrates that Berberine may play a role in protecting against CA-induced axonal transport impairment by modulating the activity of PP-2A and oxidative stress. Our findings also suggest that Berberine may be a potential therapeutic drug for AD.
Highlights
The abnormally hyperphosphorylated tau and neurofilaments (NFs) are the major proteins of neurofibrillary tangles (NFT), one of the defining hallmarks of Alzheimer’s disease (AD) [1,2]
Effects of Berberine on cell metabolism and cell viability Calyculin A (CA) was a specific inhibitor of PP-1 and phosphatase 2A (PP-2A)
We found that CA decreased cell metabolism and cell viability in a dose-dependent manner as determined by MTT and crystal violet assay (Fig. 1A)
Summary
The abnormally hyperphosphorylated tau and neurofilaments (NFs) are the major proteins of neurofibrillary tangles (NFT), one of the defining hallmarks of Alzheimer’s disease (AD) [1,2]. Phosphorylated NFs slow the velocity of transport of NFs and are shown to be involved in the pathogenesis of AD [11].
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