Additional mechanisms for brain activation failure due to reduced glucose metabolism-a commentary on Zilberter and Zilberter: The vicious circle of hypometabolism in neurodegenerative diseases

Aim: To determine the location and pattern of changes in the rate of glucose metabolism in brain structures according to positron emission tomography (PET) in patients with primary open-angle glaucoma (POAG). Methods: Nine patients with initial, developed and advanced stages of glaucoma were examined. The control group consisted of patients of a similar age group without signs of glaucoma. The PET study was performed on an Optima 560 PET / CT scanner. 30-40 minutes before the start of the scan, the patient was given an intravenous radiopharmaceutical (RP) using 18F-fluorodeoxyglucose (18F-FDG). During the accumulation of the radiopharmaceutical, the patient was in a room with dim light, with a low noise level and minimal motor activity. Results: When conducting PET with 18F-FDG, a change in the rate of glucose metabolism (RGM) was recorded in the form of a decrease in RGM in the upper parietal lobe, lower parietal lobe and precuneus (the inner part of the parietal cortex), as well as an increase in RGM of the prefrontal cortex, sensorimotor cortex. Signs of a change in RGM in the posterior region of the lumbar cortex, in the nuclei of the caudate nuclei and in the optic thalamus were also revealed. Similar data on changes in the rate of glucose metabolism in brain neurons that we recorded in patients with POAG are usually recorded in patients with other neurodegenerative diseases. Findings: Undoubtedly, the revealed changes in the rate of glucose metabolism in the neurons of the brain of patients with POAG indicate the affinity of this nosology with other neurodegenerative diseases and reveal the basis of disorders (visual, cognitive, autonomic) associated with changes in the central nervous system in patients with POAG. Research in this direction needs to be continued.

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Autophagy and ageing: implications for age-related neurodegenerative diseases

Essays in Biochemistry ◽

10.1042/bse0550119 ◽

2013 ◽

Vol 55 ◽

pp. 119-131 ◽

Cited By ~ 37

Author(s):

Bernadette Carroll ◽

Graeme Hewitt ◽

Viktor I. Korolchuk

Keyword(s):

Neurodegenerative Diseases ◽

Energy Availability ◽

Future Studies ◽

Intracellular Degradation ◽

Age Related ◽

Autophagy Induction ◽

Social Importance ◽

Cellular Dysfunction ◽

Autophagy Activity ◽

Intense Research

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our ‘ageing’ world.

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Nanotheranostic agents for neurodegenerative diseases

Emerging Topics in Life Sciences ◽

10.1042/etls20190141 ◽

2020 ◽

Vol 4 (6) ◽

pp. 645-675

Author(s):

Parasuraman Padmanabhan ◽

Mathangi Palanivel ◽

Ajay Kumar ◽

Domokos Máthé ◽

George K. Radda ◽

...

Keyword(s):

Drug Delivery ◽

Neurodegenerative Diseases ◽

Cell Types ◽

Specific Cell ◽

Ageing Population ◽

Target Tissue ◽

Therapeutic Approaches ◽

Surface Receptors ◽

Theranostic Agents ◽

Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

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