1. Parkinson's disease (PD) is considered to be an aging-related neurodegeneration of catecholamine (CA) systems [typically A9 dopamine (DA) neurons in the substantia nigra and A6 noradrenaline (NA) neurons in the locus coeruleus]. The main symptom is movement disorder caused by a DA deficiency at the nerve terminals of fibers that project from the substantia nigra to the striatum. Most PD is sporadic (sPD) without any hereditary history. sPD is speculated to be caused by some exogenous or endogenous substances that are neurotoxic toward CA neurons, which toxicity leads to mitochondrial dysfunction and subsequent oxidative stress resulting in the programmed cell death (apoptosis or autophagy) of DA neurons. 2. Recent studies on the causative genes of rare familial PD (fPD) cases, such as alpha-synuclein and parkin, suggest that dysfunction of the ubiquitin-proteasome system (UPS) and the resultant accumulation of misfolded proteins and endoplasmic reticulum stress may cause the death of DA neurons. 3. Activated microglia, which accompany an inflammatory process, are present in the nigro-striatum of the PD brain; and they produce protective or toxic substances, such as cytokines, neurotrophins, and reactive oxygen or nitrogen species. These activated microglia may be neuroprotective at first in the initial stage, and later may become neurotoxic owing to toxic change to promote the progression toward the death of CA neurons.4. All of these accumulating evidences on sPD and fPD points to a hypothesis that multiple primary causes of PD may be ultimately linked to a final common signal-transduction pathway leading to programmed cell death, i.e., apoptosis or autophagy, of the CA neurons.

We examined the activities of peptidases in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Dipeptidyl peptidase IV (DPP IV) activity was lower in synovial fluid from patients with RA, in contrast to the increase of DPP II activity in synovial fluid, as compared with OA. The DPP II/DPP IV ratio for synovial fluid was significantly higher in patients with RA than in patients with OA. A significant correlation was observed between the DPP II/DPP IV ratio for synovial fluid from patients with RA and the amount of C-reactive protein reaction. These results may be useful in the diagnosis of joint effusion of unknown origin.

We examined the activities of peptidases in plasma and tissues of the New Zealand Black (NZB) mouse as an animal model of human systemic lupus erythematosus, and also in serum from patients with rheumatoid arthritis and systemic lupus erythematosus. Activities of dipeptidyl peptidase II (DAP II) and post-proline cleaving enzyme (PPCE) were increased, and dipeptidyl peptidase IV (DAP IV) activity was decreased in plasma and spleen of NZB mice, as compared with the control BALB/c mice. Likewise, the activity of DAP II was increased and that of DAP IV was decreased in serum of patients with rheumatoid arthritis and systemic lupus erythematosus. These results indicate the importance of hydrolytic enzymes in the pathogenesis of autoimmune diseases.

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