[Frontiers in Bioscience, Scholar, 7, 189-204, June 1, 2015]

Ageing, neuroinflammation and neurodegeneration

Roberta J Ward 1, 2 , David T. Dexter 1 , Robert R. Crichton 2

1Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College, London UK. 2Universite catholique de Louvain, Belgium

TABLE OF CONTENT

1. Abstract
2. Introduction
3. Role of iron in the brain
4. Role of microglia in the brain
5. Effect of Ageing on brain iron content and neuroinflammation
    5.1. Ageing and iron accumulation
    5.2. Ageing and inflammation
6. Neurodegeneration and iron accumulation
    6.1. Iron accumulation in Parkinson’s disease
    6.2. Iron accumulation in Alzheimer’s disease
    6.3. Iron accumulation in Multiple sclerosis
    6.4. Iron accumulation in Friedreich’s ataxia
7. Neuroinflammation in neurodegenerative diseases
    7.1. Neuroinflammation in Parkinson’s disease
    7.2. Neuroinflammation in Alzheimer’s disease
    7.3. Neuroinflammation in Multiple sclerosis
8. Therapeutic strategies to reduce iron content and neuroinflammation in neurodegenerative diseases
    8.1. Chelation of excess iron in Parkinson’s disease
    8.2. Chelation of excess iron Alzheimer’s disease
    8.3. The use of anti-inflammatory drugs in neurodegenerative diseases
9. Conclusion
10. References

1. ABSTRACT

During ageing, different iron complexes accumulate in specific brain regions which are associated with motor and cognitive dysfunction. In neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, changes in local iron homoeostasis result in altered cellular iron distribution and accumulation, ultimately inducing neurotoxicity. The use of iron chelators which are able to penetrate the blood brain barrier and reduce excessive iron accumulation in specific brain regions have been shown to reduce disease progression in both Parkinson’s disease and Friedreich’s Ataxia. Neuroinflammation often occurs in neurodegenerative diseases, which is mainly sustained by activated microglia exhibiting the M1 phenotype. Such inflammation contributes to the disease progression. Therapeutic agents which reduce such inflammation, e.g. taurine compounds, may ameliorate the inflammatory process by switching the microglia from a M1 to a M2 phenotype.

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Abbreviations: PD; Parkinson’s Disease, AD-;Alzheimer’s Disease, MS;Multiple Sclerosis, FA; Friedereich Ataxia, UPDRS;Unified Parkinson’s disease rating scale, MRI;Magnetic resonance imaging, CNS, central nervous system, ROS;reactive oxygen species, Aβ; amyloid-β peptide, NFT; neurofibrillary tangles, APP; amyloid precursor protein, TLR-;Toll like receptor, COX; cyclooxygenase, LPS; lipopolysaccharide, CD;cluster of differentiation.

Key words: Iron, inflammation, Microglia Parkinson’s Disease, Alzheimer’s disease, Multiple Sclerosis, Review

Send correspondence to: Roberta J Ward, Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College, London UK, Tel: 44 207 594 6665; Fax 3210456004; E-mail Roberta.Ward@imperial.ac.uk