Detection of cutaneous prion protein deposits could help diagnose GPI-anchorless prion disease with neuropathy.

BACKGROUND AND PURPOSE: To investigate prion protein (PrP) deposits in cutaneous tissues of patients of glycosylphosphatidylinositol (GPI)-anchorless prion diseases with neuropathy. METHODS: Cutaneous tissue samples from three patients with GPI-anchorless prion diseases were obtained, two cutaneous biopsy samples from the lower leg of Case 1 (Y162X) and Case 3 (D178fs25), and a cutaneous sample taken from the abdomen during an autopsy of Case 2 (D178fs25). We performed immunohistochemistry for PrP to look for abnormal PrP deposits. RESULTS: PrP deposits were observed in the dermal papilla, the sweat glands, the hair follicles, the arrector pili muscles, and peripheral nerves of all examined cases of GPI-anchorless prion disease with neuropathy. The abnormal PrP accumulation was frequently localized at the basement membrane, and colocalized with laminin. CONCLUSION: Immunohistochemical detection of PrP in cutaneous samples could be used to definitively diagnose GPI-anchorless PrP disease with neuropathy.

Impaired antioxydative Keap1/Nrf2 system and the downstream stress protein responses in the motor neuron of ALS model mice.

The Kelch-like ECH-associated protein 1 (Keap1)/Nuclear erythroid 2-related factor 2 (Nrf2) system is the major cellular defense mechanism under oxidative stress, but the role in motor neuron degeneration under amyotrophic lateral sclerosis (ALS) pathology has not yet been fully elucidated. Here we examined temporal and spatial changes of Keap1, Nrf2, and their downstream stress response proteins heme oxgenase-1 (HO-1), glutathione, thioredoxin (TRX), and heat shock protein 70 (HSP70) throughout the course of motor neuron (MN) degeneration in the spinal cord of ALS model mice. Keap1 protein levels progressively decreased in the MN and anterior lumbar cord of ALS mice to 63% at early symptomatic 14 weeks and 58% at end symptomatic 18 weeks, while Nrf2 dramatically increased in the anterior lumbar cord with accumulation in the MN nucleus to 229% at 14 weeks and 471% at 18 weeks when glial like cells became also positive. In contrast, downstream stress response proteins such as HO-1, glutathione, TRX, and HSP70 showed only a small increase in MN with a significant increase to 149% to 280% in the number of glial-like cells after symptomatic 14 weeks. Our present observation suggests that MN selectively lost inductions of these important downstream protective proteins without regard to the Keap1/Nrf2 system activation, which could be a pivotal mechanism of neurodegenerative processes of ALS.