Reply to: Why Amyloid Is Still a Target for Alzheimer's Disease

Zhao, Hai-Lu; Huang, Yan-Mei

doi:10.1111/jgs.15827

Cited by 1 publication

(2 citation statements)

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“…The overlap of the appearance of inflammatory signs with the time of microglial activation after the Aβ immunization provides an explanation that Aβ clearance from the brain are concomitant with periods of inflammation (185). Thus, the removal of amyloid plaques may prevent it from serving its natural protective role (22) and lead to an autoimmunity impairment of brain function.…”

Section: Clearance Of Amyloid-β Plaque Provoked Autoimmune Disordersmentioning

confidence: 99%

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Amyloids in Site-Specific Autoimmune Reactions and Inflammatory Responses

et al. 2020

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Amyloid deposition is a histological hallmark of common human disorders including Alzheimer's disease (AD) and type 2 diabetes. Although some reports highlight that amyloid fibrils might activate the innate immunity system via pattern recognition receptors, here, we provide multiple lines of evidence for the protection by site-specific amyloid protein analogs and fibrils against autoimmune attacks: (1) strategies targeting clearance of the AD-related brain amyloid plaque induce high risk of deadly autoimmune destructions in subjects with cognitive dysfunction; (2) administration of amyloidogenic peptides with either full length or core hexapeptide structure consistently ameliorates signs of experimental autoimmune encephalomyelitis; (3) experimental autoimmune encephalomyelitis is exacerbated following genetic deletion of amyloid precursor proteins; (4) absence of islet amyloid coexists with T-cell-mediated insulitis in autoimmune diabetes and autoimmune polyendocrine syndrome; (5) use of islet amyloid polypeptide agonists rather than antagonists improves diabetes care; and (6) common suppressive signaling pathways by regulatory T cells are activated in both local and systemic amyloidosis. These findings indicate dual modulation activity mediated by amyloid protein monomers, oligomers, and fibrils to maintain immune homeostasis. The protection from autoimmune destruction by amyloid proteins offers a novel therapeutic approach to regenerative medicine for common degenerative diseases.

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Section: Clearance Of Amyloid-β Plaque Provoked Autoimmune Disordersmentioning

confidence: 99%

“…However, all immunotherapies targeting the clearance of amyloid under the assumption of the amyloid pathogenesis have proven unsatisfactory (18)(19)(20)(21)(22). In this framework of these treatments, immunotherapy has been historically regarded as a promising approach.…”

Section: Introductionmentioning

confidence: 99%