Multi-Targeting Neuroprotective Effects of Syzygium aromaticum Bud Extracts and Their Key Phytocompounds against Neurodegenerative Diseases.

Alzheimer's disease (AD) is a neurodegenerative disease that causes a gradual loss of normal motor and cognitive function. The complex AD pathophysiology involves various factors such as oxidative stress, neuroinflammation, amyloid-beta (Aß) aggregation, disturbed neurotransmission, and apoptosis. The available drugs suffer from a range of side effects and are not able to cover different aspects of the disease. Therefore, finding a safer therapeutic approach that can affect multiple targets at a time is highly desirable. In the present study, the underlying neuroprotective mechanism of an important culinary spice, Syzygium aromaticum (Clove) extract, and major bioactive compounds were studied in hydrogen peroxide-induced oxidative stress in human neuroblastoma SH-SY5Y cell lines as a model. The extracts were subjected to GC-MS to identify important bioactive components. The extracts and key bio-actives reduced reactive oxygen species (ROS), restored mitochondrial membrane potential (MMP), and provided neuroprotection from H2O2-induced oxidative stress in cell-based assays due to the antioxidant action. They also reduced lipid peroxidation significantly and restored GSH content. Clove extracts have also displayed anti-acetylcholinesterase (AChE) activity, anti-glycation potential, and Aß aggregation/fibrilization inhibition. The multitarget neuroprotective approach displayed by Clove makes it a potential candidate for AD drug development.

Prion Mutations in Republic of Republic of Korea, China, and Japan.

Prion gene (PRNP) mutations are associated with diverse disease phenotypes, including familiar Creutzfeldt-Jakob Disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia (FFI). Interestingly, PRNP mutations have been reported in patients diagnosed with Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease, and frontotemporal dementia. In this review, we describe prion mutations in Asian countries, including Republic of Republic of Korea, China, and Japan. Clinical phenotypes and imaging data related to these mutations have also been introduced in detail. Several prion mutations are specific to Asians and have rarely been reported in countries outside Asia. For example, PRNP V180I and M232R, which are rare in other countries, are frequently detected in Republic of Korea and Japan. PRNP T188K is common in China, and E200K is significantly more common among Libyan Jews in Israel. The A117V mutation has not been detected in any Asian population, although it is commonly reported among European GSS patients. In addition, V210I or octapeptide insertion is common among European CJD patients, but relatively rare among Asian patients. The reason for these differences may be geographical or ethical isolation. In terms of clinical phenotypes, V180I, P102L, and E200K present diverse clinical symptoms with disease duration, which could be due to other genetic and environmental influences. For example, rs189305274 in the ACO1 gene may be associated with neuroprotective effects in cases of V180I mutation, leading to longer disease survival. Additional neuroprotective variants may be possible in cases featuring the E200K mutation, such as KLKB1, KARS, NRXN2, LAMA3, or CYP4X1. E219K has been suggested to modify the disease course in cases featuring the P102L mutation, as it may result in the absence of prion protein-positive plaques in tissue stained with Congo red. However, these studies analyzed only a few patients and may be too preliminary. The findings need to be verified in studies with larger sample sizes or in other populations. It would be interesting to probe additional genetic factors that cause disease progression or act as neuroprotective factors. Further studies are needed on genetic modifiers working with prions and alterations from mutations.