Significance of intercellular communication for neurodegenerative diseases

There are different modalities of intercellular communication governed by cellular homeostasis. In this review, we will explore one of these forms of communication called extracellular vesicles (EVs). These vesicles are released by all cells in the body and are heterogeneous in nature. The primary function of EVs is to share information through their cargo consisting of proteins, lipids and nucleic acids (mRNA, miRNA, dsDNA etc.) with other cells, which have a direct consequence on their microenvironment. We will focus on the role of EVs of mesenchymal stem cells (MSCs) in the nervous system and how these participate in intercellular communication to maintain physiological function and provide neuroprotection. However, deregulation of this same communication system could play a role in several neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, multiple sclerosis, prion disease and Huntington’s disease. The release of EVs from a cell provides crucial information to what is happening inside the cell and thus could be used in diagnostics and therapy. We will discuss and explore new avenues for the clinical applications of using engineered MSC-EVs and their potential therapeutic benefit in treating neurodegenerative diseases.

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The Emerging Role of Neural Cell-Derived Exosomes in Intercellular Communication in Health and Neurodegenerative Diseases

Frontiers in Neuroscience ◽

10.3389/fnins.2021.738442 ◽

2021 ◽

Vol 15 ◽

Author(s):

Luyao Huo ◽

Xinzhe Du ◽

Xinrong Li ◽

Sha Liu ◽

Yong Xu

Keyword(s):

Neurodegenerative Diseases ◽

Intercellular Communication ◽

Neural Cells ◽

Stress Effect ◽

Brain Growth ◽

Bioactive Substances ◽

Pathological Conditions ◽

Specific Proteins ◽

The Central Nervous System

Intercellular communication in the central nervous system (CNS) is essential for brain growth, development, and homeostasis maintenance and, when dysfunctional, is involved in the occurrence and development of neurodegenerative diseases. Increasing evidence indicates that extracellular vesicles, especially exosomes, are critical mediators of intercellular signal transduction. Under physiological and pathological conditions, neural cells secret exosomes with the influence of many factors. These exosomes can carry specific proteins, lipids, nucleic acids, and other bioactive substances to the recipient cells to regulate their function. Depending on the CNS environment, as well as the origin and physiological or pathological status of parental cells, exosomes can mediate a variety of different effects, including synaptic plasticity, nutritional metabolic support, nerve regeneration, inflammatory response, anti-stress effect, cellular waste disposal, and the propagation of toxic components, playing an important role in health and neurodegenerative diseases. This review will discuss the possible roles of exosomes in CNS intercellular communication in both physiologic and neurodegenerative conditions.

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Exosomes: Innocent Bystanders or Critical Culprits in Neurodegenerative Diseases

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.635104 ◽

2021 ◽

Vol 9 ◽

Author(s):

Margarida Beatriz ◽

Rita Vilaça ◽

Carla Lopes

Keyword(s):

Neurodegenerative Diseases ◽

Intercellular Communication ◽

Prion Diseases ◽

Genetic Material ◽

Cell Communication ◽

Protein Aggregates ◽

Potential Benefits ◽

The Central Nervous System ◽

Lateral Sclerosis

Extracellular vesicles (EVs) are nano-sized membrane-enclosed particles released by cells that participate in intercellular communication through the transfer of biologic material. EVs include exosomes that are small vesicles that were initially associated with the disposal of cellular garbage; however, recent findings point toward a function as natural carriers of a wide variety of genetic material and proteins. Indeed, exosomes are vesicle mediators of intercellular communication and maintenance of cellular homeostasis. The role of exosomes in health and age-associated diseases is far from being understood, but recent evidence implicates exosomes as causative players in the spread of neurodegenerative diseases. Cells from the central nervous system (CNS) use exosomes as a strategy not only to eliminate membranes, toxic proteins, and RNA species but also to mediate short and long cell-to-cell communication as carriers of important messengers and signals. The accumulation of protein aggregates is a common pathological hallmark in many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. Protein aggregates can be removed and delivered to degradation by the endo-lysosomal pathway or can be incorporated in multivesicular bodies (MVBs) that are further released to the extracellular space as exosomes. Because exosome transport damaged cellular material, this eventually contributes to the spread of pathological misfolded proteins within the brain, thus promoting the neurodegeneration process. In this review, we focus on the role of exosomes in CNS homeostasis, their possible contribution to the development of neurodegenerative diseases, the usefulness of exosome cargo as biomarkers of disease, and the potential benefits of plasma circulating CNS-derived exosomes.

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Physiological and pathological roles of exosomes in the nervous system

BioMolecular Concepts ◽

10.1515/bmc-2015-0033 ◽

2016 ◽

Vol 7 (1) ◽

pp. 53-68 ◽

Cited By ~ 22

Author(s):

Kohei Yuyama ◽

Yasuyuki Igarashi

Keyword(s):

Alzheimer’S Disease ◽

Amyotrophic Lateral Sclerosis ◽

Nervous System ◽

Neurodegenerative Diseases ◽

Prion Disease ◽

Intercellular Communication ◽

Endosomal Membranes ◽

Nerve Development ◽

Self Repair ◽

Lateral Sclerosis

AbstractExosomes represent a subtype of extracellular nanovesicles that are generated from the luminal budding of limiting endosomal membranes and subsequent exocytosis. They encapsulate or associate with obsolete molecules to eliminate or to transfer their cargos in intercellular communication. The exosomes are also released and transported between neurons and glia in the nervous system, having a broad impact on nerve development, activation and regeneration. Accumulating evidence suggests that the exosomes are attributed to the pathogenesis of several neurodegenerative diseases such as prion disease, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, as well as aging, in which the exosomes lack the capacity for cellular self-repair and spread their enclosed pathological agents among neurons. In this article, we review the current proposed functions of exosomes in physiological and pathological processes in the nervous system.

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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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