Pro-Nerve Growth Factor Induces Activation of RhoA Kinase and Neuronal Cell Death.

We have previously shown that the expression of pro-nerve growth factor (proNGF) was significantly increased, nerve growth factor (NGF) level was decreased, and the expression of p75 was enhanced in Alzheimer's disease (AD) hippocampal samples. NGF regulates cell survival and differentiation by binding TrkA and p75 receptors. ProNGF is the precursor form of NGF, binds to p75, and induces cell apoptosis.

Polyubiquitination of the neurotrophin receptor p75 directs neuronal cell survival.

Specific binding of nerve growth factor (NGF) to p75 neurotrophin receptor (p75(NTR)) leads to p75(NTR) polyubiquitination and its subsequent interaction with TRAF6 resulting in neuronal cell survival. However, when the binding of NGF to p75(NTR) was blocked with p75 antiserum, p75(NTR) polyubiquitination and neuronal cell survival were impaired. Results showed that tyrosine phosphorylation of p75(NTR) increased the polyubiquitination of p75(NTR) and contributed to the observed apparent neuroprotective effects.

Sequestosome 1/p62: across diseases.

Sequestosome 1/p62 is a signal modulator or adaptor protein involved in receptor-mediated signal transduction. Sequestosome 1/p62 is gaining attention as it is involved in several diseases including Parkinson disease, Alzheimer disease, liver and breast cancer, Paget's disease of bone, obesity and insulin resistance. In this review, we will focus on the most recent advances on the physiological function of p62 relevant to human diseases.