Cross-Talk between Amyloid, Tau Protein and Free Radicals in Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy

Abstract

Recent years have seen remarkable progress in research into free radicals oxidative stress, particularly in the context of post-ischemic recirculation brain injury. Oxidative stress in post-ischemic tissues violates the integrity of the genome, causing DNA damage, death of neuronal, glial and vascular cells, and impaired neurological outcome after brain ischemia. Indeed, it is now known that DNA damage and repair play a key role in post-stroke white and gray matter remodeling, and restoring the integrity of the blood-brain barrier. This review will present one of the newly characterized mechanisms that emerged with genomic and proteomic development that led to brain ischemia to a new level of post-ischemic neuropathological mechanisms, such as the presence of amyloid plaques and the development of neurofibrillary tangles, which further exacerbate oxidative stress. Finally, we hypothesize that modified amyloid and the tau protein, along with the oxidative stress generated, are new key elements in the vicious circle important in the development of post-ischemic neurodegeneration in a type of Alzheimer’s disease proteinopathy.

Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation—Fantasy or Reality?

“…The development of neuroinflammatory lesions has been shown to play a key role in the progression of post-ischemic brain neurodegeneration [ 39 , 44 , 48 ]. Amyloid processing, tau protein modification, autophagy and mitophagy genes are involved in post-ischemic neurodegeneration in the same way as in Alzheimer’s disease [ 40 , 42 , 49 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ].…”

“…Restoration of blood flow in the brain following cerebral ischemia and ischemic stroke triggers an outbreak of reactive oxygen species, triggering a neuroinflammatory response and oxidative damage [ 39 , 44 , 48 , 65 ]. Reactive oxygen species destroy the membranes of neuronal and neuroglial cells, inducing lipid peroxidation, so antioxidants come into play as a therapeutic option [ 65 ].…”

“…Restoration of blood flow in the brain following cerebral ischemia and ischemic stroke triggers an outbreak of reactive oxygen species, triggering a neuroinflammatory response and oxidative damage [ 39 , 44 , 48 , 65 ]. Reactive oxygen species destroy the membranes of neuronal and neuroglial cells, inducing lipid peroxidation, so antioxidants come into play as a therapeutic option [ 65 ]. Molecular hydrogen has been recognized as an antioxidant that can buffer the destructive effects of oxidative stress in the brain following ischemia by selectively reducing cytotoxic reactive oxygen species [ 7 , 22 , 30 ].…”

“…It is now well known that ischemic neurodegeneration of the brain is caused by a set of proteomic and genetic changes that lead to the death of neuronal cells in an amyloid and tau protein dependent manner [ 40 , 46 , 47 , 56 , 57 , 58 , 59 , 63 , 64 ]. Amyloid causes oxidative stress with progressive neuroinflammation leading to brain atrophy and dementia [ 38 , 39 , 42 , 43 , 44 , 46 , 48 , 49 , 50 , 52 , 53 , 65 ]. Hard data show that cerebral ischemia in animals and humans leads to the production and accumulation of amyloid in the form of diffuse and senile plaques [ 37 , 53 , 95 , 96 , 97 , 98 , 99 ].…”

Alzheimer’s Disease Connected Genes in the Post-Ischemic Hippocampus and Temporal Cortex

“…Constantly emerging research of local or global brain ischemia (BI) provides evidence that ischemic damage is likely to be related to the etiology of Alzheimer’s disease (AD) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Stroke in clinic is a serious life-threatening vascular disease with number of complications such as: cognitive deficits, physical disability and dementia [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”