Current Pharmaceutical Design - Volume 28, Issue 37, 2022

Parkinson's disease (PD) is a common neurodegenerative disease that affects the motor system and progressively worsens with age. Current treatment options for PD mainly target symptoms, due to our limited understanding of the etiology and pathophysiology of PD. A variety of preclinical models have been developed to study different aspects of the disease. The models have been used to elucidate the pathogenesis and for testing new treatments. These models include cell models, non-mammalian models, rodent models, and non-human primate models. Over the past few decades, Caenorhabditis elegans (C. elegans) has been widely adopted as a model system due to its small size, transparent body, short generation time and life cycle, fully sequenced genome, the tractability of genetic manipulation and suitability for large scale screening for disease modifiers. Here, we review studies using C. elegans as a model for PD and highlight the strengths and limitations of the C. elegans model. Various C. elegans PD models, including neurotoxin-induced models and genetic models, are described in detail. Moreover, methodologies employed to investigate neurodegeneration and phenotypic deficits in C. elegans are summarized.

Parkinson's disease (PD) is the second most common type of neurogenerative disease among middleaged and older people, characterized by aggregation of alpha-synuclein and dopaminergic neuron loss. The microbiota- gut-brain axis is a dynamic bidirectional communication network and is involved in the pathogenesis of PD. The aggregation of misfolded protein alpha-synuclein is a neuropathological characteristic of PD, originates in the gut and migrates to the central nervous system (CNS) through the vagus nerve and olfactory bulb. The change in the architecture of gut microbiota increases the level short-chain fatty acids (SCFAs) and other metabolites, acting on the neuroendocrine system and modulating the concentrations of gamma-Aminobutyric acid (GABA), serotonin, and other neurotransmitters. It also alters the vagus and intestinal signalling, influencing the brain and behaviour by activating microglia and systemic cytokines. Both experimental and clinical reports indicate the role of intestinal dysbiosis and microbiota host interaction in neurodegeneration. Probiotics are live microorganisms that modify the gut microbiota in the small intestine to avoid neurological diseases. Probiotics have been shown in clinical and preclinical studies to be effective in the treatment of PD by balancing the gut microbiota. In this article, we described the role of gut-microbiota in the pathogenesis of PD. The article aims to explore the mechanistic strategy of the gut-brain axis and its relation with motor impairment and the use of probiotics to maintain gut microbial flora and prevent PD-like symptoms.

Over the last three decades, neurodegenerative diseases have received increasing attention due to their frequency in the aging population and the social and economic burdens they are posing. In parallel, an era’s worth of research in neuroscience has shaped our current appreciation of the complex relationship between nutrition and the central nervous system. Particular branches of nutrition continue to galvanize neuroscientists, in particular the diverse roles that bioactive food derivatives play on health and disease. Bioactive food derivatives are nowadays recognized to directly impact brain homeostasis, specifically with respect to their actions on cellular mechanisms of oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis and autophagy. However, ambiguities still exist regarding the significance of the influence of bioactive food derivatives on human health. In turn, gut microbiota dysbiosis is emerging as a novel player in the pathogenesis of neurodegenerative diseases. Currently, several routes of communication exist between the gut and the brain, where molecules are either released in the bloodstream or directly transported to the CNS. As such, bioactive food derivatives can modulate the complex ecosystem of the gut-brain axis, thus, targeting this communication network holds promises as a neuroprotective tool. This review aims at addressing one of the emerging aspects of neuroscience, particularly the interplay between food bioactive derivatives and neurodegeneration. We will specifically address the role that polyphenols and omega-3 fatty acids play in preventing neurodegenerative diseases and how dietary intervention complements available pharmacological approaches.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, with clinical manifestations of resting tremor, akinesia (or bradykinesia), rigidity, and postural instability. However, the molecular pathogenesis of PD is still unclear, and its effective treatments are limited. Substantial evidence demonstrates that long non-coding RNAs (lncRNAs) have important functions in various human diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. Therefore, the main purpose of this study is to review the role of lncRNAs in the pathogenesis of PD. Methods: The role of lncRNAs in the pathogenesis of PD is summarized by reviewing Pubmed. Results: Thirty different lncRNAs are aberrantly expressed in PD and promote or inhibit PD by mediating ubiquitin-proteasome system, autophagy-lysosomal pathway, dopamine (DA) neuronal apoptosis, mitochondrial function, oxidative stress, and neuroinflammation. Conclusion: In this direction, lncRNA may contribute to the treatment of PD as a diagnostic and therapeutic target for PD.

Pharmacokinetics (PK), as a significant part of pharmacology, runs through the overall process of the preclinical and clinical research on drugs and plays a significant role in determining the material basis of efficacy and mechanism research. However, due to the limitations of classical PK, cellular PK was put forward and developed rapidly. Many novel and original technologies have been innovatively applied to cellular PK research, thereby providing powerful technical support. As a novel field of PK research, cellular PK expands the research object and enriches the theoretical framework of PK. It provides a new perspective for elucidating the mechanism of drug action and the dynamic process of drug in the body. Furthermore, it provides a scientific basis and guiding significance for the development of new drugs and clinical rational drug use. Cellular PK can explain the dynamic process of certain drugs (e.g., antineoplastic drugs and antibiotics) and the disposition kinetics characteristics in some specific tissues (e.g., brain and tumor) in a clearer and more accurate manner. It is a beneficial supplement and the perfection of traditional PK. In the future, traditional and cellular PKs will complement each other well and improve into an all-around research system in drug developments. Briefly, this paper reviews the conceptual development of cellular PK and key associated technologies, explores its main functions and applications, and looks forward to the important pioneering significance and promising value for the development of PK.