Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

Simard, Alain R.; Rivest, Serge

doi:10.1038/sj.mp.4001809

Cited by 103 publications

(78 citation statements)

References 100 publications

(134 reference statements)

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“…Nevertheless, the initiation of EAE, and perhaps MS, requires activation of T cells in peripheral lymphoid organs and homing of myelin-reactive T cells as well as APCs to the CNS. Aided by local APCs, such as microglia and astrocytes, infiltrating T cells undergo reactivation and, in concert with other cellular and soluble components of the immune system, orchestrate the induction of CNS pathology (16,17). Mechanisms underlying the dramatic effects of nicotine in our model can be multifactorial.…”

Section: Discussionmentioning

confidence: 99%

“…Considerable evidence suggests that microglia have multiple and sometimes contrasting functions in inflammatory and degenerative disorders of the CNS (36 -40); not only can microglia only serve as APCs, but they also possess neurotoxic or neuroprotective activities (17,(41)(42)(43). The factors dictating which of these two effects are exerted by microglia are currently unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with other organ systems, the CNS has several unique properties with respect to immune responses. First, the spectrum of APCs differs from that in the periphery; in the CNS, resident microglia and astrocytes are active participants (16,17). Second, peripheral immune cells migrating into the CNS are reactivated upon encountering myelin and other Ags, enhancing their capacity to recognize a wide spectrum of ambient Ags through "determinant spreading" (18).…”

mentioning

confidence: 99%

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Nicotinic Attenuation of Central Nervous System Inflammation and Autoimmunity

Shi¹,

Piao²,

Kuo

et al. 2009

The Journal of Immunology

121

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The expression of nicotinic acetylcholine receptors by neurons, microglia, and astrocytes suggests possibly diverse mechanisms by which natural nicotinic cholinergic signaling and exposure to nicotine could modulate immune responses within the CNS. In this study, we show that nicotine exposure significantly delays and attenuates inflammatory and autoimmune responses to myelin Ags in the mouse experimental autoimmune encephalomyelitis model. In the periphery, nicotine exposure inhibits the proliferation of autoreactive T cells and alters the cytokine profile of helper T cells. In the CNS, nicotine exposure selectively reduces numbers of CD11c+ dendritic and CD11b+ infiltrating monocytes and resident microglial cells and down-regulates the expression of MHC class II, CD80, and CD86 molecules on these cells. The results underscore roles of nicotinic acetylcholine receptors and nicotinic cholinergic signaling in inflammatory and immune responses and suggest novel therapeutic options for the treatment of inflammatory and autoimmune disorders, including those that affect the CNS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Nicotinic Attenuation of Central Nervous System Inflammation and Autoimmunity

Shi¹,

Piao²,

Kuo

et al. 2009

The Journal of Immunology

121

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“…Moreover, the abilities of BMM to cross BBB was also investigated (87)(88)(89)(90)(91)(92)(93)(94). In particular, it was demonstrated that monocytes infiltrate the brain in the MPTP mouse model of PD (91)(92)(93).…”

Section: Discussionmentioning

confidence: 99%

A Macrophage−Nanozyme Delivery System for Parkinson's Disease

et al. 2007

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Selective delivery of antioxidants to the substantia nigra pars compacta (SNpc) during Parkinson's disease (PD) can potentially attenuate oxidative stress and as such increase survival of dopaminergic neurons. To this end, we developed a bone-marrow-derived macrophage (BMM) system to deliver catalase to PD-affected brain regions in an animal model of human disease. To preclude BMMmediated enzyme degradation, catalase was packaged into a block ionomer complex with a cationic block copolymer, polyethyleneimine-poly(ethylene glycol) (PEI-PEG). The self-assembled catalase/ PEI-PEG complexes, "nanozymes", were ca. 60 to 100 nm in size, stable in pH and ionic strength, and retained antioxidant activities. Cytotoxicity was negligible over a range of physiologic nanozyme concentrations. Nanozyme particles were rapidly, 40-60 min, taken up by BMM, retained catalytic activity, and released in active form for greater than 24 h. In contrast, "naked" catalase was rapidly degraded. The released enzyme decomposed microglial hydrogen peroxide following nitrated alphasynuclein or tumor necrosis factor alpha activation. Following adoptive transfer of nanozyme-loaded BMM to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-intoxicated mice, ca. 0.6% of the injected dose were found in brain. We conclude that cell-mediated delivery of nanozymes can reduce oxidative stress in laboratory and animal models of PD.

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“…Amyloid beta monomer treats as normal by immune system with no response but after aggregation large amount of polymers as isomers confuse the immune system, which it responds like as foreign particle and activates immune cells as well as mass inflammation [10]. In the AD, occurred increasing the filtration of blood derived microglial cells, which could be good therapeutic approach for preventing the formation of beta amyloid deposits [11].…”

Section: Role Of Immune System In Admentioning

confidence: 99%