Unmet needs of patients with Parkinson's disease: interview survey of patients and caregivers.

We performed a 20-item questionnaire-based interview of 132 patients with Parkinson's disease (PD): 81 patients with Hoehn & Yahr (H&Y) stage I - III PD, and 51 caregivers of patients with H&Y stage IV - V PD, to evaluate patient and caregiver satisfaction with PD treatment. The survey revealed that PD patients often experience non-motor symptoms, which are not adequately alleviated by antiparkinsonian agents. Furthermore, PD patients want their physicians to listen to them and take their concerns seriously, to explain their disease comprehensively, and to provide the latest information on PD and its treatment. Both patients and caregivers agreed on anxiety toward the future, communication difficulties, and their different movement pace; however, there were differences in their relative perceptions of various aspects of daily care. The evaluation revealed that PD patients have unmet needs in their treatment and standards of care. Areas for future improvement as highlighted in this study include: the development of better treatment for motor symptoms, the development of new treatments for non-motor symptoms and improved two-way communication between patient and physician.

Parkin is associated with cellular vesicles.

We recently identified a novel gene, parkin, as a pathogenic gene for autosomal recessive juvenile parkinsonism. Parkin encodes a 52-kDa protein with a ubiquitin-like domain and two RING-finger motifs. To provide a insight into the function of parkin, we have examined its intracellular distribution in cultured cells. We found that parkin was localized in the trans-Golgi network and the secretory vesicles in U-373MG or SH-SY5Y cells by immunocytochemical analyses. In the subsequent subcellular fractionation studies of rat brain, we showed that parkin was copurified with the synaptic vesicles (SVs) when we used low ionic conditions throughout the procedure. An immunoelectromicroscopic analysis indicated that parkin was present on the SV membrane. Parkin was readily released from SVs into the soluble phase by increasing ionic strength at neutral pH, but not by a non-ionic detergent. To elucidate its responsible region for membrane association, we transfected with green fluorescent protein-tagged deletion mutants of parkin into COS-1 cells followed by subcellular fractionation. We demonstrated the ability of parkin to bind to the membranes through a broad region except for the ubiquitin-like domain. The significance of SV localization of parkin is discussed.

Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase.

Autosomal recessive juvenile parkinsonism (AR-JP), one of the most common familial forms of Parkinson disease, is characterized by selective dopaminergic neural cell death and the absence of the Lewy body, a cytoplasmic inclusion body consisting of aggregates of abnormally accumulated proteins. We previously cloned PARK2, mutations of which cause AR-JP (ref. 2), but the function of the gene product, parkin, remains unknown. We report here that parkin is involved in protein degradation as a ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7, and that mutant parkins from AR-JP patients show loss of the ubiquitin-protein ligase activity. Our findings indicate that accumulation of proteins that have yet to be identified causes a selective neural cell death without formation of Lewy bodies. Our findings should enhance the exploration of the molecular mechanisms of neurodegeneration in Parkinson disease as well as in other neurodegenerative diseases that are characterized by involvement of abnormal protein ubiquitination, including Alzheimer disease, other tauopathies, CAG triplet repeat disorders and amyotrophic lateral sclerosis.