The p38 MAP kinase signaling pathway in Alzheimer's disease

In conclusion, there is overwhelming evidence that phospho-p38 immunoreactivity is significantly increased in AD brain. Although there are some disagreements between the studies in terms of exactly where phospho-p38 is found in AD brain, this is actually secondary to the finding that phospho-p38 is increased in areas of AD brain that are affected by the disease. There is increasing evidence that inhibiting p38 activity may be an important therapeutic strategy in the treatment of brain disease or injury. For example, inhibition of p38 activity significantly attenuates brain injury and neurological deficits after cerebral focal ischemia [3]. One of minocycline’s therapeutic targets includes p38 inhibition, and minocycline has been demonstrated to decrease disease progression in a mouse model of amyotrophic lateral sclerosis [60] and attenuate dopaminergic neuronal cell death in the MPTP model of Parkinson’s disease [12]. These and other findings clearly indicate that p38 inhibition may provide a rationale drug target for the treatment of AD, as well as other neurodegenerative conditions.