Press Release | Autophagy and Mitochondria: Targets in Neurodegenerative Disorders (image)

 

Autophagy is a cellular degradation process that can cause the death of a cell in certain conditions. Autophagy is necessary to maintain cellular homeostasis by clearing out damaged cellular organelles and proteins through certain pathways. Mitochondria are cell organelles responsible for the constant supply of energy to maintain cellular physiology and energy metabolism.

Ashutosh Kumar et al. at the National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, India present a review on autophagy in neuronal cells. The researchers believe that autophagy on the neuronal cells can lead to neurodegenerative diseases and countering the effects of this process through targeted drugs can be beneficial in the fight against such diseases. Neuronal cells are more vulnerable to such bioenergetic depletion as most of their function crucially depends on availability of energy derived mainly from mitochondrial function. Any incidence of mitochondrial dysfunction inevitably results in neurodegeneration. Therefore, mitochondrial autophagy (mitophagy) plays an integral role in the onset of neurodegenerative diseases as the instance and failure of these pathways can have destructive effects on cellular homeostasis.

Previous studies show significant association between neurodegenerative disorders and mitochondrial dysfunction and abnormal mitophagy. Abnormal mitophagy leads to the accumulation of protein aggregates and consequential neurodegeneration. Future treatments for neurodegenerative disorders could involve drugs targeting mitochondria and autophagy-related proteins and enzymes. This review discusses the involvement of mitochondrial and autophagy dysfunction in neurodegenerative disorders specifically focusing on Alzheimer’s, Parkinson’s, and Huntington’s disease. Read full press release to find out more at: https://www.eurekalert.org/pub_releases/2018-12/bsp-aam122618.php

 

 

This article by Dr. Ashutosh Kumar et al. is published in CNS & Neurological Disorders – Drug Targets, Volume 17, Issue 9, 2018. The article is Open Access till 31st January, 2019. To obtain the article, please visit: http://www.eurekaselect.com/164678

OPEN ACCESS ARTICLE – Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer – Current Neurovascular Research

Journal: Current Neurovascular Research

Author(s):  Kenneth Maiese

Abstract:

Background: The mammalian circadian clock and its associated clock genes are increasingly been recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease.

Methods: In light of the significant role circadian rhythm can hold over the body’s normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis.

Results: In experimental models, lifespan is significantly reduced with the introduction of arrhythmic mutants and leads to an increase in oxidative stress exposure. Interestingly, patients with Alzheimer’s disease and Parkinson’s disease may suffer disease onset or progression as a result of alterations in the DNA methylation of clock genes as well as prolonged pharmacological treatment for these disorders that may lead to impairment of circadian rhythm function. Tumorigenesis also can occur with the loss of a maintained circadian rhythm and lead to an increased risk for nasopharyngeal carcinoma, breast cancer, and metastatic colorectal cancer. Interestingly, the circadian clock system relies upon the regulation of the critical pathways of autophagy, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) as well as proliferative mechanisms that involve the wingless pathway of Wnt/β-catenin pathway to foster cell survival during injury and block tumor cell growth.

Conclusion: Future targeting of the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm may hold the key for the development of novel and effective therapies against aging- related disorders, neurodegenerative disease, and tumorigenesis.

Read more here: http://www.eurekaselect.com/154252

Article by Disease – “Brain Aging and Disorders of the Central Nervous System: Kynurenines and Drug Metabolism”

Article by Disease on “Metabolic Disorders”

Abstract:

Introduction: The kynurenine pathway includes several neuroactive compounds, including kynurenic acid, picolinic acid, 3-hydroxykynurenine and quinolinic acid. The enzymatic cascade of the kynurenine pathway is tightly connected with the immune system, and may provide a link between the immune system and neurotransmission.

Main Areas Covered: Alterations in this cascade are associated with neurodegenerative, neurocognitive, autoimmune and psychiatric disorders, such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, migraine or schizophrenia.

Highlights: This review highlights the alterations in this metabolic pathway in the physiological aging process and in different disorders. A survey is also presented of therapeutic possibilities of influencing this metabolic route, which can be achieved through the use of synthetic kynurenic acid analogues, enzyme inhibitors or even nanotechnology.

Read more: http://www.eurekaselect.com/node/138027/article