Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease

Alzheimer disease (AD) is the most prevalent neurodegenerative disease in the elderly, characterized by accumulation in the brain of misfolded proteins, inflammation, and oxidative damage leading to neuronal cell death. By considering the viewpoint that AD onset and worsening may be influenced by environmental factors causing infection, oxidative stress, and inflammatory reaction, we investigated the changes of the salivary proteome in a population of patients with respect to that in healthy controls (HCs). Indeed, the possible use of saliva as a diagnostic tool has been explored in several oral and systemic diseases. Moreover, the oral cavity continuously established adaptative and protective processes toward exogenous stimuli. In the present study, qualitative/quantitative variations of 56 salivary proteoforms, including post-translationally modified derivatives, have been analyzed by RP-HPLC-ESI-IT-MS and MS/MS analyses, and immunological methods were applied to validate MS results. The salivary protein profile of AD patients was characterized by significantly higher levels of some multifaceted proteins and peptides that were either specific to the oral cavity or also expressed in other body districts: (i) peptides involved in the homeostasis of the oral cavity; (ii) proteins acting as ROS/RNS scavengers and with a neuroprotective role, such as S100A8, S100A9, and their glutathionylated and nitrosylated proteoforms; cystatin B and glutathionylated and dimeric derivatives; (iii) proteins with antimicrobial activity, such as α-defensins, cystatins A and B, histatin 1, statherin, and thymosin β4, this last with a neuroprotective role at the level of microglia. These results suggested that, in response to injured conditions, Alzheimer patients established defensive mechanisms detectable at the oral level. Data are available via ProteomeXchange with identifier PXD021538.

Download Full-text

Salivary protein roles in oral health and as predictors of caries risk

Open Life Sciences ◽

10.1515/biol-2018-0023 ◽

2018 ◽

Vol 13 (1) ◽

pp. 174-200

Author(s):

Galina Laputková ◽

Vladimíra Schwartzová ◽

Juraj Bánovčin ◽

Michal Alexovič ◽

Ján Sabo

Keyword(s):

Dental Caries ◽

Oral Cavity ◽

Human Saliva ◽

Salivary Protein ◽

Oral Diseases ◽

Irreversible Damage ◽

Current State ◽

Whole Saliva ◽

State Of Research ◽

Insight Into

AbstractThis work describes the current state of research on the potential relationship between protein content in human saliva and dental caries, which remains among the most common oral diseases and causes irreversible damage in the oral cavity. An understanding the whole saliva proteome in the oral cavity could serve as a prerequisite to obtaining insight into the etiology of tooth decay at early stages. To date, however, there is no comprehensive evidence showing that salivary proteins could serve as potential indicators for the early diagnosis of the risk factors causing dental caries. Therefore, proteomics indicates the promising direction of future investigations of such factors, including diagnosis and thus prevention in dental therapy.

Download Full-text

Host Defense Proteins Derived from Human Saliva Bind to Staphylococcus aureus

Infection and Immunity ◽

10.1128/iai.00825-12 ◽

2013 ◽

Vol 81 (4) ◽

pp. 1364-1373 ◽

Cited By ~ 24

Author(s):

Seok-Mo Heo ◽

Kyoung-Soo Choi ◽

Latif A. Kazim ◽

Molakala S. Reddy ◽

Elaine M. Haase ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Oral Cavity ◽

Host Defense ◽

Bacterial Colonization ◽

Human Saliva ◽

Salivary Protein ◽

Salivary Proteins ◽

Staphylococcal Protein A ◽

Defense Proteins ◽

Content Type

ABSTRACTProteins in human saliva are thought to modulate bacterial colonization of the oral cavity. Yet, information is sparse on how salivary proteins interact with systemic pathogens that transiently or permanently colonize the oral environment.Staphylococcus aureusis a pathogen that frequently colonizes the oral cavity and can cause respiratory disease in hospitalized patients at risk. Here, we investigated salivary protein binding to this organism upon exposure to saliva as a first step toward understanding the mechanism by which the organism can colonize the oral cavity of vulnerable patients. By using fluorescently labeled saliva and proteomic techniques, we demonstrated selective binding of major salivary components byS. aureusto include DMBT1gp-340, mucin-7, secretory component, immunoglobulin A, immunoglobulin G, S100-A9, and lysozyme C. Biofilm-grownS. aureusstrains bound fewer salivary components than in the planctonic state, particularly less salivary immunoglobulins. A corresponding adhesive component on theS. aureussurface responsible for binding salivary immunoglobulins was identified as staphylococcal protein A (SpA). However, SpA did not mediate binding of nonimmunoglobulin components, including mucin-7, indicating the involvement of additional bacterial surface adhesive components. These findings demonstrate that a limited number of salivary proteins, many of which are associated with various aspects of host defense, selectively bind toS. aureusand lead us to propose a possible role of saliva in colonization of the human mouth by this pathogen.

Download Full-text

Mechanisms of Perinatal Arterial Ischemic Stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.41 ◽

2014 ◽

Vol 34 (6) ◽

pp. 921-932 ◽

Cited By ~ 62

Author(s):

David Fernández-López ◽

Niranjana Natarajan ◽

Stephen Ashwal ◽

Zinaida S Vexler

Keyword(s):

Neuronal Cell Death ◽

Neuronal Cell ◽

The Elderly ◽

Experimental Models ◽

Adult Brain ◽

Clinical Aspects ◽

Long Term Effects ◽

Arterial Ischemic Stroke ◽

Perinatal Stroke

The incidence of perinatal stroke is high, similar to that in the elderly, and produces a significant morbidity and severe long-term neurologic and cognitive deficits, including cerebral palsy, epilepsy, neuropsychological impairments, and behavioral disorders. Emerging clinical data and data from experimental models of cerebral ischemia in neonatal rodents have shown that the pathophysiology of perinatal brain damage is multifactorial. These studies have revealed that, far from just being a smaller version of the adult brain, the neonatal brain is unique with a very particular and age-dependent responsiveness to hypoxia–ischemia and focal arterial stroke. In this review, we discuss fundamental clinical aspects of perinatal stroke as well as some of the most recent and relevant findings regarding the susceptibility of specific brain cell populations to injury, the dynamics and the mechanisms of neuronal cell death in injured neonates, the responses of neonatal blood-brain barrier to stroke in relation to systemic and local inflammation, and the long-term effects of stroke on angiogenesis and neurogenesis. Finally, we address translational strategies currently being considered for neonatal stroke as well as treatments that might effectively enhance repair later after injury.

Download Full-text