Trans - and Cis -Phosphorylated Tau Protein: New Pieces of the Puzzle in the Development of Neurofibrillary Tangles in Post-Ischemic Brain Neurodegeneration of the Alzheimer's Disease-like Type

• Published in: International journal of molecular sciences Vol. 25; no. 6; p. 3091
• Main Authors: Pluta, Ryszard, Czuczwar, Stanisław J
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.03.2024; MDPI
• Subjects: Alzheimer Disease - metabolism; Alzheimer’s disease; Animals; Brain - metabolism; brain ischemia; Brain Ischemia - metabolism; cardiac arrest; cis-phosphorylated tau protein; Dementia; Disability; Disease; Gene expression; Humans; hyperphosphorylation; Ischemia; Neurodegeneration; Neurofibrillary Tangles - metabolism; Neuropathology; Pathology; Phosphorylation; Proteins; Stroke; tau protein; tau Proteins - metabolism; Traumatic brain injury; brain ischemia; trans-phosphorylated tau protein; Alzheimer’s disease; cis-phosphorylated tau protein; genes; hyperphosphorylation; neurofibrillary tangles; paired helical filaments; cardiac arrest; tau protein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25063091

Recent evidence indicates that experimental brain ischemia leads to dementia with an Alzheimer's disease-like type phenotype and genotype. Based on the above evidence, it was hypothesized that brain ischemia may contribute to the development of Alzheimer's disease. Brain ischemia and Alzheimer's disease are two diseases characterized by similar changes in the hippocampus that are closely related to memory impairment. Following brain ischemia in animals and humans, the presence of amyloid plaques in the extracellular space and intracellular neurofibrillary tangles was revealed. The phenomenon of tau protein hyperphosphorylation is a similar pathological feature of both post-ischemic brain injury and Alzheimer's disease. In Alzheimer's disease, the phosphorylated Thr231 motif in tau protein has two distinct and conformations and is the primary site of tau protein phosphorylation in the pre-entanglement cascade and acts as an early precursor of tau protein neuropathology in the form of neurofibrillary tangles. Based on the latest publication, we present a similar mechanism of the formation of neurofibrillary tangles after brain ischemia as in Alzheimer's disease, established on - and -phosphorylation of tau protein, which ultimately influences the development of tauopathy.