Functions and distribution of calpain-calpastatin system components in brain during mammal ontogeny.

Calpain and calpastatin are the key components of the calcium-dependent proteolytic system. Calpains are regulatory, calcium-dependent, cytoplasmic proteinases, and calpastatin is the endogenous inhibitor of calpains. Due to the correlation between changes in the activity of the calpain-calpastatin system in the brain and central nervous system (CNS) pathology states, this proteolytic system is a prime focus of research on CNS pathological processes, generally characterized by calpain activity upregulation. The present review aims to generalize existing data on cerebral calpain distribution and function through mammalian ontogenesis. Special attention is given to the most recent studies on the topic as more information on calpain-calpastatin system involvement in normal CNS development and functioning has become available. We also discuss data on calpain and calpastatin activity and production in different brain regions during ontogenesis as comparative analysis of these results in association with ontogeny processes can reveal brain regions and developmental stages with pronounced function of the calpain system.

Neurotensin-Binding Immunoglobulin G in Patients with Parkinson's Disease.

INTRODUCTION: Neurotensin (NTS) is a 13-amino acid neuropeptide functionally linked with the brain dopaminergic system via expression of the NTS peptide or its receptor in dopamine neurons. Neuropeptide-binding immunoglobulins (Igs) are present in humans and can be involved in both physiological and pathological processes. Considering the functional link between NTS and dopamine neurons, we studied the occurrence of NTS-binding IgG autoantibodies in patients with Parkinson's disease (PD). METHODS: Plasma levels of NTS-binding IgG were analyzed using enzyme-linked immunosorbent assay in both male and female PD patents and in age-matched healthy controls. Possible microbial origin of NTS cross-reactive IgG was analyzed by sequence alignment of the 6-amino acid C-terminal NTS pharmacophore with bacterial and viral proteins from the public NCBI database. RESULTS: NTS-binding IgG were detected in the plasma of all study subjects, while their levels were consistently lower in PD patients versus controls (p = 0.0001), independently from age or sex of the study participants. Moreover, PD patients with a more severe stage (2.5-3.0) of the disease had lower levels of NTS-binding IgG (p = 0.0004) than those with a milder stage (1.0-2.0). Furthermore, PD patients taking amantadine or high doses of levodopa had higher levels of NTS-binding IgG than those without medication. Contiguous sequence homology for the NTS pharmacophore was present in several microbial proteins occurring in human gut microbiota. DISCUSSION: The study revealed that NTS-binding IgG occur naturally in humans and that PD patients display their low plasma levels accentuated by disease severity. The functional significance of this finding and its relevance to the pathophysiology of PD, including putative link to gut microbiota, remain to be studied.