scholarly journals The cellular pathways of neuronal autophagy and their implication in neurodegenerative diseases

2009 ◽  
Vol 1793 (9) ◽  
pp. 1496-1507 ◽  
Author(s):  
Zhenyu Yue ◽  
Lauren Friedman ◽  
Masaaki Komatsu ◽  
Keiji Tanaka
Keyword(s):  
Neurodegenerative Diseases ◽  
Cellular Pathways ◽  
Neuronal Autophagy

scholarly journals Molecular and cellular pathways contributing to brain aging

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Aliabbas Zia ◽  
Ali Mohammad Pourbagher-Shahri ◽  
Tahereh Farkhondeh ◽  
Saeed Samarghandian
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Brain Aging ◽  
Neuroprotective Effect ◽  
Ros Generation ◽  
Brain Health ◽  
Cellular Pathways ◽  
Aging Mechanisms ◽  
Oxidatively Modified ◽  
Biology Of Aging

AbstractAging is the leading risk factor for several age-associated diseases such as neurodegenerative diseases. Understanding the biology of aging mechanisms is essential to the pursuit of brain health. In this regard, brain aging is defined by a gradual decrease in neurophysiological functions, impaired adaptive neuroplasticity, dysregulation of neuronal Ca2+ homeostasis, neuroinflammation, and oxidatively modified molecules and organelles. Numerous pathways lead to brain aging, including increased oxidative stress, inflammation, disturbances in energy metabolism such as deregulated autophagy, mitochondrial dysfunction, and IGF-1, mTOR, ROS, AMPK, SIRTs, and p53 as central modulators of the metabolic control, connecting aging to the pathways, which lead to neurodegenerative disorders. Also, calorie restriction (CR), physical exercise, and mental activities can extend lifespan and increase nervous system resistance to age-associated neurodegenerative diseases. The neuroprotective effect of CR involves increased protection against ROS generation, maintenance of cellular Ca2+ homeostasis, and inhibition of apoptosis. The recent evidence about the modem molecular and cellular methods in neurobiology to brain aging is exhibiting a significant potential in brain cells for adaptation to aging and resistance to neurodegenerative disorders.

scholarly journals Misfolded protein aggregation and altered cellular pathways in neurodegenerative diseases

STEMedicine ◽  
2020 ◽  
Vol 1 (4) ◽  
pp. e63
Author(s):  
Huifang Li ◽  
Zhenghong Yu ◽  
Wei Zhang
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Cell Types ◽  
World Health ◽  
Protein Homeostasis ◽  
Sensory Impairments ◽  
Cellular Pathways ◽  
Health Organization ◽  
Nonhuman Species ◽  
Human Death

Neurodegenerative diseases are estimated by the World Health Organization to be the second leading cause of human death by 2050. They actually are a group of chronic neurological disorders leading to motor, cognitive and sensory impairments in both human and nonhuman species. Despite different in clinical manifestation, prevalence, risk factors, cell types injured and genes hijacked, neurodegenerative disorders are usually associated with the misfolding and aggregation of a distinct protein that accumulates in diverse cellular locations including the nucleus, cytoplasm, plasma membrane and extracellular space. Here we intend to give an overview of the characters and features of several pathogenic protein aggregates in disease brains, and introduce some general signaling pathways involved in protein homeostasis with emphasis on their puzzling roles under the degenerative conditions.

scholarly journals Alteration of Sphingolipids in Biofluids: Implications for Neurodegenerative Diseases

2019 ◽  
Vol 20 (14) ◽  
pp. 3564 ◽  
Author(s):  
Luciana M. Pujol-Lereis
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Option ◽  
Acyl Chain ◽  
Comprehensive Review ◽  
Cellular Processes ◽  
Acyl Chain Length ◽  
Sphingosine 1 Phosphate ◽  
Cellular Pathways ◽  
Specific Species ◽  
The Impact

Sphingolipids (SL) modulate several cellular processes including cell death, proliferation and autophagy. The conversion of sphingomyelin (SM) to ceramide and the balance between ceramide and sphingosine-1-phosphate (S1P), also known as the SL rheostat, have been associated with oxidative stress and neurodegeneration. Research in the last decade has focused on the possibility of targeting the SL metabolism as a therapeutic option; and SL levels in biofluids, including serum, plasma, and cerebrospinal fluid (CSF), have been measured in several neurodegenerative diseases with the aim of finding a diagnostic or prognostic marker. Previous reviews focused on results from diseases such as Alzheimer’s Disease (AD), evaluated total SL or species levels in human biofluids, post-mortem tissues and/or animal models. However, a comprehensive review of SL alterations comparing results from several neurodegenerative diseases is lacking. The present work compiles data from circulating sphingolipidomic studies and attempts to elucidate a possible connection between certain SL species and neurodegeneration processes. Furthermore, the effects of ceramide species according to their acyl-chain length in cellular pathways such as apoptosis and proliferation are discussed in order to understand the impact of the level alteration in specific species. Finally, enzymatic regulations and the possible influence of insulin resistance in the level alteration of SL are evaluated.

scholarly journals Neuronal autophagy and neurodegenerative diseases

2012 ◽  
Vol 44 (2) ◽  
pp. 89 ◽  
Author(s):  
Jin H. Son ◽  
Jung Hee Shim ◽  
Kyung-Hee Kim ◽  
Ji-Young Ha ◽  
Ji Young Han
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuronal Autophagy

scholarly journals Regulation of Membrane Phospholipid Homeostasis in Neurodegenerative Diseases

2020 ◽  
Vol 05 (03) ◽  
pp. 1-1
Author(s):  
XinRan Quan ◽  
◽  
Marica Bakovic ◽  
Keyword(s):  
Neurodegenerative Diseases ◽  
Symptom Management ◽  
Neuronal Loss ◽  
World Population ◽  
Cellular Processes ◽  
World Population Growth ◽  
The World ◽  
Present Rate ◽  
Neuronal Signal ◽  
Cellular Pathways

Neurodegenerative diseases (NDs) are a diverse group of neuropathological diseases that are currently incurable due to the irreversible neuronal loss. At the present rate of the world population growth, it is projected that the number of ND cases will double by the year of 2050. With treatments only available for symptom management and relief, disease prevention may yield significant benefits. Recently, there had been association drawn between the disruption of phospholipid (PL) homeostasis and the progression of NDs. Pathological developments were observed in cellular processes including autophagy, maintenance of mitochondrial integrity, and management of tissue oxidative stress. As PLs actively participate in the regulation of these cellular pathways and in neuronal signal transduction for the maintenance of an optimally functioning nervous system, their homeostasis is tightly controlled via an intricate system of interconversion and metabolism. Therefore, in this review, the contribution of a homeostatic PL pool and the detrimental effects by the lack thereof, are discussed in detail as it relates to ND development.

scholarly journals Common molecular mechanisms underlie the transfer of alpha-synuclein, Tau and huntingtin and modulate spontaneous activity in neuronal cells

2021 ◽  
Author(s):  
Ines Caldeira Bras ◽  
Mohammad Hossein Khani ◽  
Eftychia Vasili ◽  
Wiebke Mobius ◽  
Dietmar Riedel ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuronal Activity ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Neuronal Cells ◽  
Alpha Synuclein ◽  
Free Form ◽  
Polyglutamine Expansion ◽  
Associated Proteins ◽  
Cellular Pathways

The misfolding and accumulation of disease-related proteins are common hallmarks among several neurodegenerative diseases. Alpha-synuclein (aSyn), Tau and huntingtin (wild-type and mutant, 25QHtt and 103QHtt, respectively) were recently shown to be transferred from cell-to-cell through different cellular pathways, thereby contributing to disease progression and neurodegeneration. However, the relative contribution of each of these mechanisms towards the spreading of these different proteins and the overall effect on neuronal function is still unclear. To address this, we exploited different cell-based systems to conduct a systematic comparison of the mechanisms of release of aSyn, Tau and Htt, and evaluated the effects of each protein upon internalization in microglial, astrocytic, and neuronal cells. In the models used, we demonstrate that 25QHtt, aSyn and Tau are released to the extracellular space at higher levels than 103QHtt, and their release can be further augmented with the co-expression of USP19. Furthermore, cortical neurons treated with recombinant monomeric 43QHtt exhibited alterations in neuronal activity that correlated with the toxicity of the polyglutamine expansion. Tau internalization resulted in an increase in neuronal activity, in contrast to slight effects observed with aSyn. Interestingly, all these disease-associated proteins were present at higher levels in ectosomes than in exosomes. The internalization of both types of extracellular vesicles (EVs) by microglial or astrocytic cells elicited the production of pro-inflammatory cytokines and promoted an increase in autophagy markers. Additionally, the uptake of the EVs modulated neuronal activity in cortical neurons. Overall, our systematic study demonstrates the release of neurodegenerative disease-associated proteins through similar cellular pathways. Furthermore, it emphasizes that protein release, both in a free form or in EVs, might contribute to a variety of detrimental effects in receiving cells and to progression of pathology, suggesting they may be exploited as valid targets for therapeutic intervention in different neurodegenerative diseases.

scholarly journals CRISPRi screens in human astrocytes elucidate regulators of distinct inflammatory reactive states

2021 ◽  
Author(s):  
Kun Leng ◽  
Brendan Rooney ◽  
Hyosung Kim ◽  
Wenlong Xia ◽  
Mark Koontz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Interferon Signaling ◽  
Human Astrocytes ◽  
Cellular Pathways ◽  
Human Ipsc ◽  
Ischemic Encephalopathy

ABSTRACTIn response to central nervous system injury or disease, astrocytes become reactive, adopting context-dependent states with altered functions. Certain inflammatory insults induce reactive astrocyte states that lose homeostatic functions and gain harmful outputs, and likely contribute to neuroinflammatory and neurodegenerative diseases. However, the cellular pathways controlling these states are not fully understood. Here, we combined single-cell transcriptomics with CRISPRi screening in human iPSC-derived astrocytes to systematically interrogate inflammatory reactivity. We found that autocrine-paracrine IL-6 and interferon signaling downstream of canonical NF-κB activation drove two distinct inflammatory reactive states promoted by and inhibited by STAT3, respectively. Furthermore, these states corresponded with those observed in other experimental contexts, including in vivo, and their markers were upregulated in the human brain in Alzheimer’s disease and hypoxic ischemic encephalopathy. These results and the platform we established have the potential to guide the development of therapeutics to selectively modulate different aspects of inflammatory astrocyte reactivity.

scholarly journals O-GlcNAcylation in health and neurodegenerative diseases

2021 ◽  
Author(s):  
Byeong Eun Lee ◽  
Pann-Ghill Suh ◽  
Jae-Ick Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Posttranslational Modification ◽  
Protein Modification ◽  
Molecular Mechanisms ◽  
The Body ◽  
Neuroprotective Effects ◽  
Functional Roles ◽  
Cellular Pathways ◽  
Neuronal Functions ◽  
The Brain

AbstractO-GlcNAcylation is a posttranslational modification that adds O-linked β-N-acetylglucosamine (O-GlcNAc) to serine or threonine residues of many proteins. This protein modification interacts with key cellular pathways involved in transcription, translation, and proteostasis. Although ubiquitous throughout the body, O-GlcNAc is particularly abundant in the brain, and various proteins commonly found at synapses are O-GlcNAcylated. Recent studies have demonstrated that the modulation of O-GlcNAc in the brain alters synaptic and neuronal functions. Furthermore, altered brain O-GlcNAcylation is associated with either the etiology or pathology of numerous neurodegenerative diseases, while the manipulation of O-GlcNAc exerts neuroprotective effects against these diseases. Although the detailed molecular mechanisms underlying the functional roles of O-GlcNAcylation in the brain remain unclear, O-GlcNAcylation is critical for regulating diverse neural functions, and its levels change during normal and pathological aging. In this review, we will highlight the functional importance of O-GlcNAcylation in the brain and neurodegenerative diseases.

scholarly journals Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases

2020 ◽  
Vol 21 (19) ◽  
pp. 7174 ◽  
Author(s):  
Fang Luo ◽  
Aaron F. Sandhu ◽  
Wiramon Rungratanawanich ◽  
George E. Williams ◽  
Mohammed Akbar ◽  
...  
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Protective Mechanism ◽  
Biological Functions ◽  
Metabolism Regulation ◽  
Wide Range ◽  
Immune Enhancement ◽  
Lateral Sclerosis ◽  
Neuronal Autophagy

With aging, the nervous system gradually undergoes degeneration. Increased oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and cell death are considered to be common pathophysiological mechanisms of various neurodegenerative diseases (NDDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), organophosphate-induced delayed neuropathy (OPIDN), and amyotrophic lateral sclerosis (ALS). Autophagy is a cellular basic metabolic process that degrades the aggregated or misfolded proteins and abnormal organelles in cells. The abnormal regulation of neuronal autophagy is accompanied by the accumulation and deposition of irregular proteins, leading to changes in neuron homeostasis and neurodegeneration. Autophagy exhibits both a protective mechanism and a damage pathway related to programmed cell death. Because of its “double-edged sword”, autophagy plays an important role in neurological damage and NDDs including AD, PD, HD, OPIDN, and ALS. Melatonin is a neuroendocrine hormone mainly synthesized in the pineal gland and exhibits a wide range of biological functions, such as sleep control, regulating circadian rhythm, immune enhancement, metabolism regulation, antioxidant, anti-aging, and anti-tumor effects. It can prevent cell death, reduce inflammation, block calcium channels, etc. In this review, we briefly discuss the neuroprotective role of melatonin against various NDDs via regulating autophagy, which could be a new field for future translational research and clinical studies to discover preventive or therapeutic agents for many NDDs.

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