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Iron Metabolism & Neurodegenerative Diseases

Published on: 22 Jul 2022 Viewed: 73

Our staff editors continue to share brilliant, thoughtful, and meaningful topics and articles in this recommended series.

This week, we would like to share several the latest articles on anxiety and depression related to Iron Metabolism & Neurodegenerative Diseases.

Title: 'Fly-ing' from rare to common neurodegenerative disease mechanisms
Authors: Mengqi Ma, Matthew J. Moulton, Shenzhao Lu, Hugo J. Bellen
Type: Review
Highlights:
The study of rare neurological disease using the fruit fly, Drosophila melanogaster, has shed valuable insight into common neurodegenerative diseases including AD and PD.

Mitochondrial dysfunction and lipid dysregulation are shared features of many rare neurological disorders and common neurodegenerative diseases.

Studies aimed at delineating mechanisms in flies have shed light on disease pathogenesis and have identified novel therapeutic targets for the treatment of neurological disease.

Advances in genome sequencing have enabled researchers and clinicians to probe vast numbers of human variants to distinguish pathogenic from benign variants. Model organisms have been crucial in variant assessment and in delineating the molecular mechanisms of some of the diseases caused by these variants. The fruit fly, Drosophila melanogaster, has played a valuable role in this endeavor, taking advantage of its genetic technologies and established biological knowledge. We highlight the utility of the fly in studying the function of genes associated with rare neurological diseases that have led to a better understanding of common disease mechanisms. We emphasize that shared themes emerge among disease mechanisms, including the importance of lipids, in two prominent neurodegenerative diseases: Alzheimer's disease (AD) and Parkinson's disease (PD).
Access this article: https://doi.org/10.1016/j.tig.2022.03.018


Title: Repositioning and development of new treatments for neurodegenerative diseases: Focus on neuroinflammation
Authors: Bruno Dutra Arbo, Lucia Emanueli Schimith, Michele Goulart dos Santos, Mariana Appel Hort
Type: Review
Abstract: 
Neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, are characterized by the progressive loss of neuronal cells, resulting in different clinical symptoms according to the affected brain region. Although there are drugs available for the treatment of these diseases, they present relatively low efficacy and are not capable of modifying the course of the disease or stopping its progression. In the field of drug development, drug repurposing could be an interesting strategy to search new therapeutic options against neurodegenerative diseases, since it involves lower costs and time for development. In this review, we discuss the search of new treatments for Alzheimer's and Parkinson's disease through drug repurposing. A focus was given to drugs that modulate neuroinflammation, since it represents a common point among neurodegenerative diseases and has been explored as a target for drug action.
Access this article: https://doi.org/10.1016/j.ejphar.2022.174800


Title: Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases
Authors: Gurjit Kaur Bhatti, Anshika Gupta, Paras Pahwa, Naina Khullar, Satwinder Singh, Umashanker Navik, Shashank Kumar, Sarabjit Singh Mastana, Arubala P. Reddy, P. Hemachandra Reddy, Jasvinder Singh Bhatti
Type: Review
Abstract: 
Mitochondria are the organelles that generate energy for the cells and act as biosynthetic and bioenergetic factories, vital for normal cell functioning and human health. Mitochondrial bioenergetics is considered an important measure to assess the pathogenesis of various diseases. Dysfunctional mitochondria affect or cause several conditions involving the most energy-intensive organs, including the brain, muscles, heart, and liver. This dysfunction may be attributed to an alteration in mitochondrial enzymes, increased oxidative stress, impairment of electron transport chain and oxidative phosphorylation, or mutations in mitochondrial DNA that leads to the pathophysiology of various pathological conditions, including neurological and metabolic disorders. The drugs or compounds targeting mitochondria are considered more effective and safer for treating these diseases. In this review, we make an effort to concise the available literature on mitochondrial bioenergetics in various conditions and the therapeutic potential of various drugs/compounds targeting mitochondrial bioenergetics in metabolic and neurodegenerative diseases.
Access this article: https://doi.org/10.1016/j.bj.2022.05.002


Title: Mitochondria research and neurodegenerative diseases: On the track to understanding the biological world of high complexity
Authors: Daniela Mendes, Francisco Peixoto, Maria M. Oliveira, Paula B. Andrade, Romeu A. Videira
Type: Review
Highlights:
●The way how the emergence of mitochondria research field improved our knowledge on the hmajor metabolic pathways.
●How mitochondria 3-D architecture fits with different cellular and physiological functions.
●Putative interlink between mitochondrial dysfunction and neurodegeneration – the cases of AD and PD.
●Strategies to develop a mitochondria-targeted therapy for neurodegenerative diseases.
Abstract:
From the simple unicellular eukaryote to the highly complex multicellular organism like Human, mitochondrion emerges as a ubiquitous player to ensure the organism’s functionality. It is popularly known as “the powerhouse of the cell” by its key role in ATP generation. However, our understanding of the physiological relevance of mitochondria is being challenged by data obtained in different fields. In this review, a short history of the mitochondria research field is presented, stressing the findings and questions that allowed the knowledge advances, and put mitochondrion as the main player of safeguarding organism life as well as a key to solve the puzzle of the neurodegenerative diseases.
Access this article: https://doi.org/10.1016/j.mito.2022.05.001


Title: Brain drug delivery and neurodegenerative diseases: Polymeric PLGA-based nanoparticles as a forefront platform
Authors: Miguel Pinto, Vera Silva, Sandra Barreiro, Renata Silva, Fernando Remião, Fernanda Borges, Carlos Fernandes
Type: Review
Highlights:
●Neurodegenerative diseases (NDs) etiology remains largely misunderstood.
●Current drugs are only palliative and struggle to modify diseases progression.
●Drug Delivery using PLGA nanoparticles can be used to improve drug’s efficacy.
●Encapsulated drugs showed to be more effective in in vivo models.
Abstract:
The discovery of effective drugs for the treatment of neurodegenerative disorders (NDs) is a deadlock. Due to their complex etiology and high heterogeneity, progresses in the development of novel NDs therapies have been slow, raising social/economic and medical concerns. Nanotechnology and nanomedicine evolved exponentially in recent years and presented a panoply of tools projected to improve diagnosis and treatment. Drug-loaded nanosystems, particularly nanoparticles (NPs), were successfully used to address numerous drug glitches, such as efficacy, bioavailability and safety. Polymeric nanoparticles (PNPs), mainly based on polylactic-co-glycolic acid (PLGA), have been already validated and approved for the treatment of cancer, neurologic dysfunctions and hormonal-related diseases. Despite promising no PNPs-based therapy for neurodegenerative disorders is available up to date. To stimulate the research in the area the studies performed so far with polylactic-co-glycolic acid (PLGA) nanoparticles as well as the techniques aimed to improve PNPs BBB permeability and drug targeting were revised. Bearing in mind NDs pharmacological therapy landscape huge efforts must be done in finding new therapeutic solutions along with the translation of the most promising results to the clinic, which hopefully will converge in the development of effective drugs in a foreseeable future.
Access this article: https://doi.org/10.1016/j.arr.2022.101658


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