Cited by 206Neuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and TreatmentsTryptophan and brain disorders

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Inflammatory Mechanisms and Oxidative Stress as Key Factors Responsible for Progression of Neurodegeneration: Role of Brain Innate Immune System

Leszek, Jerzy, E. Barreto, George, G|siorowski, Kazimierz, Koutsouraki, Euphrosyni, Ávila-Rodrigues, Marco, Aliev, Gjumrakch·2016·CNS & Neurological Disorders - Drug Targets

DOI 10.2174/1871527315666160202125914

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Abstract

Chronic inflammation is characterized by longstanding microglial activation followed by sustained release of inflammatory mediators, which aid in enhanced nitrosative and oxidative stress. The sustained release of inflammatory mediators propels the inflammatory cycle by increased microglial activation, promoting their proliferation and thus stimulating enhanced release of inflammatory factors. Elevated levels of several cytokines and chronic neuroinflammation have been associated with many neurodegenerative disorders of central nervous system like age-related macular degeneration, Alzheimer disease, multiple sclerosis, Parkinson's disease, Huntington' disease, and tauopathies. This review highlights the basic mechanisms of neuroinflammation, the characteristics of neurodegenerative diseases, and the main immunologic responses in CNS neurodegenerative disorders. A comprehensive outline for the crucial role of microglia in neuroinflammation and neurodegeneration and the role of Toll-like receptor signalling in coexistence of inflammatory mechanisms and oxidative stress as major factors responsible for progression of neurodegeneration have also been presented.

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“During the early and late phases of AD physiopathology, producing reactive oxygen species and nitrogen intermediates such as nitric oxides (NO) and peroxynitrite can cause neuronal damages.(12) Therefore, treatments with antioxidants such as vitamin E, minocycline, and resveratrol (RV) could protect neurons from OS/NS…”
Background
Mesoporous Silica Particles are Phagocytosed by Microglia and Induce a Mild Inflammatory Response In Vitro
Sala‐Jarque, J., García-Lara, E., Carreras-Dominguez, P., Zhou, C., Rabaneda‐Lombarte, N., Solà, C., Vidal-Taboada, J. M., Feiler, A. A., Abrahamsson, N., Kozlova, E. N., et al. (2022) · Nanomedicine · doi:10.2217/nnm-2022-0026 · Cited by 1
The role of astrocytes response triggered by hyperglycaemia during spinal cord injury
Sámano, C., & Mazzone, G. L. (2023) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2023.2264538 · Cited by 2
“…(Kimelberg and Nedergaard 2010, lawrence et al. 2023), along with glial scar formation and dysregulation of excitatory amino acids (lau and Yu 2001, leszek et al. 2016). the lack of AtP is another serious consequence related to the mechanisms of ROS-induced glutamate uptake blockade in astrocytes…”
An Investigation of the Inflammatory Landscape in the Brain and Bone Marrow of the APP/PS1 Mouse
Chittimalli, K., Adkins, S., Arora, S., Singh, J., & Jarajapu, Y. P. R. (2024) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-240024 · Cited by 1
The impact of electronic cigarette aerosol exposure on spatial memory formation: Modulation by orally administered vitamin E
Yaseen, A. A., Alzoubi, K. H., Al‐Sawalha, N. A., et al. (2024) · NeuroToxicology · doi:10.1016/j.neuro.2024.10.014 · Cited by 1
Correlación entre el grado de hipertensión arterial y el índice de estrés oxidativo. Estudio de cohorte en una población de pacientes hipertensos sistémicos en República Dominicana
Nuñez-Musa, R. A., Sellés, A. J. N., Rossi, W. M., Marmolejos, R. G., & Martı́nez-Sánchez, G. (2019) · Ciencia y Salud · doi:10.22206/cysa.2019.v3i2.pp17-33 · Cited by 1
Monomeric and Dimeric Bromophenols from the Red Alga Ceramium Sp. with Antioxidant and Anti-Inflammatory ActivitiesPreprint
Zhang, Y., Glukhov, E., Yu, H., Gerwick, L. G., Dorrestein, P. C., & Gerwick, W. H. (2020) · ChemRxiv · doi:10.26434/chemrxiv.12760352.v1 · Cited by 1
“…as Alzheimer’s disease and Parkinson’s disease, metabolic disorders like obesity, diabetes and cardiovascular diseases, as well as others (Alfadda and Sallam, 2012; Franceschi and Campisi, 2014; Leszek et al., 2016; McBean et al., 2017; Rani et al., 2016; Reuter et al., 2010; Siti et al., 2015).”
Background
Marine Fungal Metabolite Butyrolactone I Prevents Cognitive Deficits and Inflammation Evoked by AlCl3 in zebrafishPreprint
Nie, Y., Yang, J., Liang, J., Yang, Z., Zhou, L., Liu, Y., Ma, X., Qian, Z., Hong, P., Kalueff, A. V., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-685780/v1 · Cited by 1
Peer Review #1 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.1)"
(2018) · PeerJ · doi:10.7287/peerj.4756v0.1/reviews/1
Peer Review #1 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.3)"
(2018) · PeerJ · doi:10.7287/peerj.4756v0.3/reviews/1
Peer Review #1 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.2)"
(2018) · PeerJ · doi:10.7287/peerj.4756v0.2/reviews/1
Peer Review #3 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.2)"
(2018) · PeerJ · doi:10.7287/peerj.4756v0.2/reviews/3
Peer Review #3 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.1)"
(2018) · PeerJ · doi:10.7287/peerj.4756v0.1/reviews/3
Hippocampal Astrocyte Response to Melatonin Following Neural Damage Induction in Rat
Babaee, A., Eftekhar‐Vaghefi, S. H., Asadi‐Shekaari, M., Shahrokhi, N., Dehghani-Soltani, S., & Basiri, M. (2019) · Basic and Clinical Neuroscience Journal · doi:10.32598/bcn.9.10.415
Peer Review #2 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.1)"
(2018) · PeerJ · doi:10.7287/peerj.4756v0.1/reviews/2
Peer Review #2 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.2)"
(2018) · PeerJ · doi:10.7287/peerj.4756v0.2/reviews/2
Peer Review #4 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.2)"
(2018) · PeerJ · doi:10.7287/peerj.4756v0.2/reviews/4
Peer Review #4 of "A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants (v0.1)"
(2018) · PeerJ · doi:10.7287/peerj.4756v0.1/reviews/4
Efecto protector de la tibolona en un modelo inflamatorio de microglía estimulado por palmitato
Hidalgo‐Lanussa, O. (2020) · Repositorio Institucional (Pontificia Universidad Javeriana) · doi:10.11144/javeriana.10554.38564
Unveiling Sex-based Differences in Parkinson's Disease: A Comprehensive Meta-analysis of Transcriptomic StudiesPreprint
López‐Cerdán, A., Andreu, Z., Hidalgo, M. R., Grillo-Risco, R., Català-Senent, J. F., Soler-Sáez, I., Neva-Alejo, A., Gordillo, F., de la Iglesia-Vayá, M., & Garcia‐García, F. (2022) · Research Square · doi:10.21203/rs.3.rs-2058256/v1
Multiple Mechanisms of the Therapeutic Effect of Trehalose in Inhibition of Experimental Neurodegeneration
Pupyshev, A. B., Короленко, Т. А., & Tikhonova, M. A. (2023) · Нейрохимия · doi:10.31857/s1027813323040192
RNA-sequencing Reveals Altered Gene Expression in the Ventromedial Hypothalamus Following Predator Odor Exposure
Shemery, A., Gibson, M., Gorrell, E., Daniel, D., Piontkivska, H., & Novak, C. M. (2024) · F1000Research · doi:10.12688/f1000research.152034.1
Integration of transcriptomics and metabolomics to study the mechanism of Siwei Huangqi powder in Tibetan medicine for protecting against high-altitude hypoxic brain injuries
Cao, W., Guo, J., Zhang, N., et al. (2024) · Journal of Traditional and Complementary Medicine · doi:10.1016/j.jtcme.2024.11.002
“5,15,16 The pathological results of our study revealed that SWHQP significantly reduced brain tissue inflammation and the brain water content after intervention; moreover, SWHQP had a good antihypoxic effect on HHBI.”
Mechanism of therapeutic action of Folium Artemisiae Argyi on Neuropathic pain based on network pharmacology and molecular docking technology
Deng, J., Li, J., Azhar, M., et al. (2024) · Food, Nutrition and Health. · doi:10.1007/s44403-024-00008-7
Exploratory Data Analysis of the In Vitro Effects of Novel Hydrazide-Hydrazone Antioxidants in the Context of In Silico Predictors
Yordanov, Y., Tzankova, V., Stefanova, D., Georgieva, M., & Tzankova, D. (2025) · Antioxidants · doi:10.3390/antiox14050566
Ozone-induced Neurotoxicity: Mechanistic Insights and Implications for Neurodegenerative Diseases
Bjørklund, G., Gurgas, L., & Hangan, T. (2025) · Current Medicinal Chemistry · doi:10.2174/0109298673375058250624070823
The role of lipid profile and inflammotry markers in diffrentiating between focal and generalized types of seizures in pediatric epilepsy patients
Bilge, S., & Bilgin, H. (2025) · The European Research Journal · doi:10.18621/eurj.1745159
Hypothesis-Driven Insights and Clinical Trial Updates in Alzheimer’s Disease Pathogenesis
Alhawarri, M. B. (2025) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273387383250924031644
Thiamine Reverses Monoaminergic, Oxidative, and Inflammatory Dysregulation in a Rat Model of Adolescent Ethanol Withdrawal
Haidary, M., Ansari, M., Ansari, S., Rezayee, H., Hanifi, S., & Hossaini, D. (2025) · Alcoholism Treatment Quarterly · doi:10.1080/07347324.2025.2603655
Additional file 1 of Nilotinib modulates LPS-induced cognitive impairment and neuroinflammatory responses by regulating P38/STAT3 signaling
Kim, J., Lee, H.-J., Park, J.-H., Cha, B.-Y., & Hoe, H.-S. (2022) · Figshare · doi:10.6084/m9.figshare.20329567
Additional file 1 of Marine fungal metabolite butyrolactone I prevents cognitive deficits by relieving inflammation and intestinal microbiota imbalance on aluminum trichloride-injured zebrafish
Nie, Y., Yang, J., Zhou, L., Yang, Z., Liang, J., Liu, Y., Ma, X., Qian, Z., Hong, P., Kalueff, A. V., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19136068
Brain Volume Alterations and Cognitive Functions in Patients with Common Variable Immunodeficiency: Evaluating the Impact of Autoimmunity
Aykan, F. S., Saygın, D. A., Çölkesen, F., Poyraz, N., Evcen, R., Kılınç, M., Yıldız, E., Önalan, T., Akkuş, F. A., Çelik, E. E., et al. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15020503
“This phenomenon can be explained by more aggressive immune dysregulation, the cerebral effects of systemic inflammation, and neuroinflammatory processes associated with autoimmunity [51].”
Virus-induced changes in peroxisomal markers among HIV-infected patients
Butorov, E. V. (2026) · RUDN Journal of Medicine · doi:10.22363/2313-0245-2025-30-1-124-138
Translational evidence for increased central amygdala IL-6 activity in alcohol dependence
Onge, C. M. S., Erikson, C. M., Cruz, B., Borgonetti, V., Hashimoto, J. G., Cucinello‐Ragland, J. A., Fitzpatrick‐Schmidt, T., Rodriguez, L., Khom, S., Palmisano, M., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03868-2 · Cited by 1
Plant‐Based Brain Therapies
Padma, K. R., Don, K. R., Sankari, M., Harathi, K., & Sandhya, N. (2026) · Wiley eBooks · doi:10.1002/9781394360260.ch15
Nutritional Regulation of Neuro-Inflammation: Mechanisms, Evidence, and Public Health Benefits
Kumar, R., Aves, M., & Kaur, H. (2026) · Current Research in Nutrition and Food Science Journal · doi:10.12944/crnfsj.14.special-issue-june.03

Authors: Leszek, J., E. Barreto, G., G|siorowski, K., Koutsouraki, E., Ávila-Rodrigues, M., & Aliev, G.
ORCID: Leszek, Jerzy
Aliev, Gjumrakch
Venue: CNS & Neurological Disorders - Drug Targets
Publisher: Bentham Science Publishers Ltd.
Published: 2016-03-10
Volume: 15
Issue: 3
Pages: 329-336
ISSN: 1568-007X (ISSN-L)
1871-5273
DOI: 10.2174/1871527315666160202125914
OpenAlex: W2271123303
Semantic Scholar: 91475bee1cf3d32abe2d7e1be1755b559ca3dc93
Cited by: 206
References: 88
Citations by year: 2026: 13 · 2025: 19 · 2024: 23 · 2023: 16 · 2022: 13 · 2021: 23 · 2020: 20 · 2019: 16 · 2018: 31 · 2017: 23 · 2016: 9
FWCI: 14.41
Type: journal article
Language: en
Open access: closed
Locations: CNS & Neurological Disorders - Drug Targets (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: neuroinflammation, neurodegeneration, microglial activation, oxidative stress, nitrosative stress, Toll-like receptor signaling, cytokines, Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, age-related macular degeneration, tauopathy
MeSH terms: Animals, Brain, Humans, Immunity, Innate, Inflammation, Cytokines, Microglia, Oxidative Stress, Disease Progression, Neurodegenerative Diseases

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Inflammatory Mechanisms and Oxidative Stress as Key Factors Responsible for Progression of Neurodegeneration: Role of Brain Innate Immune System

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