Case Report: A Case of a Patient with Smith-Magenis Syndrome and Early-Onset Parkinson's Disease.

Smith-Magenis Syndrome (SMS) is a rare genetic disorder, characterized by intellectual disability (ID), behavioral impairments, and sleep disturbances, as well as multiple organ anomalies in some affected individuals. The syndrome is caused by a deletion in the chromosome band around 17p11.2, including the Retinoic Acid Induced 1 (RAI1) gene, a multifaceted transcriptional regulator that modulates the expression of genes involved in cellular proliferation and neurodevelopment. This gene has a positive role in regulating BDNF and, importantly, affects several cell mechanisms and pathways such as the nigro-striatal pathway, which is crucial for motor function. Parkinson's disease (PD) is one of the most common neurodegenerative diseases in older populations. It is characterized by various physical symptoms including tremors, loss of balance, bradykinesia, and a stooping posture. We present a case study of a patient diagnosed with both SMS and early-onset PD (at the age of 49). The association between both conditions is as yet ambiguous. Genome-wide association studies (GWAS) implicate an association between the RAI1 gene and PD. Similarly, the co-existence of both SMS and PD in the patient suggests a possible association between RAI1 copy number variations (CNVs) and PD, further indicating that RAI1 has strong implications for PD pathogenesis. Our results suggest that RAI1 CNVs and the pathophysiology of PD may be related, underscoring the need for further research in this field. Therefore, caregivers of SMS patients should pay careful attention to the possibility of their patients developing EOPD and should consider starting treatment for PD as soon as the first symptoms appear.

PKCtheta is required for hemostasis and positive regulation of thrombin-induced platelet aggregation and alpha-granule secretion.

Platelet activation due to vascular injury is essential for hemostatic plug formation, and is mediated by agonists, such as thrombin, which trigger distinct receptor-coupled signaling pathways. Thrombin is a coagulation protease, which activates G protein-coupled protease-activated receptors (PARs) on the surface of platelets. We found that C57BL/6J and BALB/C mice that are deficient in protein kinase C theta (PKCtheta), exhibit an impaired hemostasis, and prolonged bleeding following vascular injury. In addition, murine platelets deficient in PKCtheta displayed an impaired thrombin-induced platelet activation and aggregation response. Lack of PKCtheta also resulted in impaired alpha-granule secretion, as demonstrated by the low surface expression of CD62P, in thrombin-stimulated platelets. Since PAR4 is the only mouse PAR receptor that delivers thrombin-induced activation signals in platelets, our results suggest that PKCtheta is a critical effector molecule in the PAR4-linked signaling pathways and in the regulation of normal hemostasis in mice.

Protein kinase C-theta in platelet activation.

Members of the protein kinase C (PKC) family of serine/threonine kinases have been implicated in several physiological processes regulating the activation response of platelets. They are involved in processes leading to granule secretion, integrin activation, platelet aggregation and spreading, and procoagulation. The protein kinase C θ (PKCθ) isoform, which was originally identified in T lymphocytes, is also expressed at relatively high levels in platelets, wherein it is involved in the regulation of hemostasis and thrombosis. Recent studies suggest a role for PKCθ in protease-activated receptor (PAR)-, glycoprotein VI (GPVI) receptor- and glycoprotein α(IIb)ß(3) integrin receptor-linked signal transduction pathways. The present review focuses on the latest observations relevant to the role of PKCθ in platelet activation.