Neurodegenerative proteinopathies associated with neuroinfections

Abstract

Infectious agents, including viruses and bacteria, are proposed to be involved in the pathogenesis of Alzheimer’s disease (AD). According to this hypothesis, these agents have capacity to evade the host immune system leading to chronic infection, inflammation, and subsequent deposition of Aβ and phosphorylated-tau in the brain. Co-existing proteinopathies and age-related pathologies are common in AD and the brains of elderly individuals, but whether these are also related to neuroinfections remain to be established. This study determined the prevalence and distribution of neurodegenerative proteinopathies in patients with infection-induced acute or chronic inflammation associated with herpes simplex virus (HSV) encephalitis ( n = 13) and neurosyphilis ( n = 23). The mean age at death in HSV patients was 53 ± 12 years (range 24–65 years) and survival was 9 days–6 years following initial infection. The mean age at death and survival in neurosyphilis patients was 60 ± 15 years (range 36–86 years) and 1–5 years, respectively. Neuronal tau-immunoreactivity and neurites were observed in 8 HSV patients and 19 neurosyphilis patients, and in approximately half of these, this was found in regions associated with inflammation and expanding beyond regions expected from the Braak stage of neurofibrillary degeneration. Five neurosyphilis patients had cortical ageing-related tau astrogliopathy. Aβ-plaques were found in 4 HSV patients and 11 neurosyphilis patients. Lewy bodies were observed in one HSV patient and two neurosyphilis patients. TDP-43 pathology was absent. These observations provide insights into deposition of neurodegenerative proteins in neuroinfections, which might have implications for COVID-19 patients with chronic and/or post-infectious neurological symptoms and encephalitis. Supplementary Information The online version contains supplementary material available at 10.1007/s00702-021-02371-7.

West Nile Virus Neuroinfection in Humans: Peripheral Biomarkers of Neuroinflammation and Neuronal Damage

“…Indeed, biomarkers are under intensive investigation as potential predictors of neurological impairments (neurodegenerative diseases or encephalitis) and severe long-term effects, and could in turn orient patient care early upon admission [64][65][66]. Neurodegeneration and/or the modulation of neurodegenerative mechanisms are hallmarks of numerous viral brain infections [27]. Indeed, it is now accepted that viral agents could be considered risk factors in the etiology of some neurodegenerative diseases [27,67,68].…”

“…To date, several studies and case reports have suggested long-term consequences of WNV infection, such as prolonged fatigue until six months after infection [23], WNV retinopathy [24], or prolonged neuromuscular symptoms [25]. Persistent neuroinflammation in WNND patients could also affect the development of neurodegenerative diseases [26,27]. The ability to predict clinical evolution to either recovery or CNS involvement has not been yet elucidated.…”

Synthesis and evaluation of cerebroprotective activity of novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives containing residues of amino acids and dipeptides

“…2.1.1. General procedure for synthesis of amides of 2amino-4,5-dimethoxybenzoic acid (3,4) 0.05 mol of the acetyl chloride or benzoyl chloride was slowly added to a solution of 9.85 g (0.05 mol) of 2-amino-4,5-dimethoxybenzoic acid (2) in 35 ml of 10% sodium hydroxide with stirring. As a result, a precipitate was formed, which was filtered and washed with water.…”

“…Every year there is an increase in patients with various cognitive impairments, which defines the urgency of developing new methods of their treatment. The main causes of cognitive dysfunctions are vascular pathologies (cerebral ischemia [1]), neurodegenerative processes (such as in the case of Alzheimer's disease) [2], traumatic brain injuries [3] and neuroinfections [4]. It is worth noting that disorders of cerebral circulation are the second most common cause of cognitive dysfunction after Alzheimer's disease [5].…”

“…Some novel compounds of allyl/benzyl quinazolinone displayed remarkable anti-inflammatory activity as compared to Diclofenac sodium [16]. Also, different 2,7-disubstituted[1, 3,4]-tiadiazolov[2,3b]quinazolin-5(4H)-ones were synthesized, and they showed good anti-inflammatory activity [17]. Various 2-(3aryl-1H-pyrazol-1-yl)benzo[d]thiazole incorporated fused thiazolo [2,3-b]quinazolinones exhibited prominent anticancer and antibacterial activities.…”