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Molecular Basis of Etiological Implications in Alzheimer’s Disease: Focus on Neuroinflammation

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Abstract

Significant bodies of evidences have shown different mechanisms known to be the etiological cause of Alzheimer’s disease (AD) involving amyloid-beta protein accumulation, chronic inflammatory reactions, oxidative stress, proteasome inhibition, and high-cholesterol level, but the presize etiology of AD still remains enigmatic. Recent studies indicate that these mechanisms seem to be interlinked, and neuroinflammation emerges as a major regulatory and commen factor in all these mechanisms. In amyloid-beta protein, induced neurodegenerative hypothesis of AD inflammatory cytokines IFN-γ, TNF-α, interleukin (IL)-1α plays an important role in the progression of the disease. In cholesterol induced hypothesis liver X receptor mediated IL-4 also plays a major role in the progression of neuroinflammation. Notably, Omi and HtrA2 proteases play very important functions in neuronal dysfunction, which may lead to neurodegeneration. Further at genetic level, alterations in the genes occur especially in APP, PSEN1, PSEN2, APO E(ε4), ADAM12, and SH3MD1 which mediate neurodegeneration. Additionaly, The role of SP-1, NF-κB, and BCAE-1 is critical in the regulation of neuroinflammation-associated disease pathogenesis. All together, in this review, we discus the importance of neuroinflammatory mediators and their mechanistic role in the process of AD neurodegeneration.

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Abbreviations

NGF:

Nerve growth factor

GDNF:

Glial cell line-derived neurotrophic factor

MANF:

Mesencephalic astrocyte-derived neurotrophic factor

bFGF:

Basic fibroblast growth factor

PD:

Parkinson’s disease

AD:

Alzheimer’s disease

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

TNF-α:

Tumor necrosis factor-α

NF-κB:

Nuclear factor kappa-B

COX-2:

Cyclooxygenase-2

GFAP:

Glial fibrillary acidic protein

CHOP:

C/EBP, homologous protein 10

iNOS:

Inducible nitric oxide synthase

MDA:

Malondialdehyde

IL-1α:

Interleukin-1α

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

P-p38 MAPK:

Phosphorylated p38 mitogen-activated protein kinase

NO:

Nitric oxide

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Acknowledgments

The lab space provided by Dr. Anil Mishra, professor in Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University, Cleveland, OH, USA is greatfully acknowledged.

Competing Interests

There are no conflicts of interest because Dr. Rituraj Niranjan is the sole auther in the manuscript.

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  1. Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University, 2109 Adelbert Rd., BRB 501, Cleveland, OH, 44106, USA

    Rituraj Niranjan

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Niranjan, R. Molecular Basis of Etiological Implications in Alzheimer’s Disease: Focus on Neuroinflammation. Mol Neurobiol 48, 412–428 (2013). https://doi.org/10.1007/s12035-013-8428-4

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