![]() ![]() Hence, a high systemic dose is required to reach therapeutic levels within the brain, which leads to adverse effects. These barriers limit the target efficiency of therapeutic drugs for brain and neuronal mitochondria. Typically, almost no macromolecular or small molecule drugs (>98%) are able to reach CNS because of factors, including reduced drug diffusion through the blood-brain barrier (BBB), lipophilic nature of drugs, and high negative potential of the mitochondria. However, the target efficiency of most drugs for the mitochondria in brain parenchyma is quite limited, which affects the therapeutic effects in central nervous system (CNS) diseases. Therefore, neuronal mitochondria may be a potential treatment target for NDs. In postmortem analysis of spinal cord samples from amyotrophic lateral sclerosis (ALS) patients, reduced mitochondrial DNA (mtDNA) copy number and defective respiratory chain activity were found. ![]() In addition, mitochondria isolated from cortical tissue obtained postmortem from Huntington's disease (HD) patients showed ultrastructural abnormalities. In brain samples obtained post-mortem from PD patients, the mitochondrial respiratory chain was found to be dysfunctional. Moreover, most familial Parkinson's disease (PD) loci are directly related to the mitochondria. For instance, mitochondrial dysfunction induces the accumulation of phosphorylated tau (p-tau) and Aβ in Alzheimer's disease (AD). Hence, impaired mitochondrial function can radically alter cell and tissue homeostasis.Ī growing number of studies have suggested that mitochondrial dysfunction occurs in healthy aging and diseases, especially neurodegenerative diseases (NDs). In addition, mitochondria are involved in key cellular processes such as calcium homeostasis, generation of reactive oxidation species (ROS), initiation of apoptosis, and release of metabolites to control cell fate and function. It is best known as the primary production site of the cellular adenosine triphosphate (ATP), and is responsible for energy distribution throughout the cell. It is an essential organelle for most eukaryotic cells, and plays a crucial role in cell survival/death. Mitochondrion is one of the largest organelles in human cells, occupying approximately 25% of the cytoplasmic volume. Finally, we summarized the evidence and possible use for the promising role of NP-based theranostic systems in the treatment of mitochondrial dysfunction-related NDs. We also reviewed the use and advantages of various NPs (including organic, inorganic, and biological membrane-coated NPs) for the treatment and diagnosis of NDs. ![]() In this review, we discussed the role of dysfunctional mitochondria in ND pathogenesis as well as the physiological barriers to various treatment strategies. Owing to their adjustable size, appropriate charge, and lipophilic surface, nanoparticles (NPs) are the ideal theranostic system for crossing the BBB and targeting the neuronal mitochondria. Among them, nanotechnology-based treatments show especially promising results. Therefore, a variety of neuron mitochondrial targeting strategies has been developed. Several obstacles, including the blood-brain barrier (BBB) and cell/mitochondrial membranes, reduce the efficiency of drug entry into the target lesions. Mitochondria play an important role in oxidative balance and metabolic activity of neurons therefore, mitochondrial dysfunction is associated with NDs and mitochondria are considered a potential treatment target for NDs. Neurodegenerative diseases (NDs) are a class of heterogeneous diseases that includes Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |