The gut microbiota coevolves with its host, and numerous factors like diet, lifestyle, drug intake and geographical location continuously modify its composition, deeply influencing host health. Recent studies demonstrated that gut dysbiosis can alter normal brain function through the so-called gut-brain axis, a bidirectional communication network between the central nervous system and the gastrointestinal tract, thus playing a key role in the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). In this perspective, in the constant search for novel treatments in AD, the rational modulation of gut microbiota composition could represent a promising approach to prevent or delay AD onset or to counteract its progression. Preclinical and human studies on microbiota modulation through oral bacteriotherapy and faecal transplantation showed antiinflammatory and antioxidant effects, upregulation of plasma concentration of neuroprotective hormones, restoration of impaired proteolytic pathways, amelioration of energy homeostasis with consequent decrease of AD molecular hallmarks and improvement of behavioural and cognitive performances. In this review, we dissect the role of gut microbiota in AD and highlight recent advances in the development of new multitarget strategies for microbiota modulation to be used as possible preventative and therapeutic approaches in AD.

Alzheimer's disease (AD) is a progressive neurodegeneration characterized by neuron death ending in memory and cognitive decline. A major concern in AD research is the identification of new therapeutics that could prevent or delay the onset of the disorder, with current treatments being effective only in reducing symptoms. In this perspective, the use of engineered probiotics as therapeutic tools for the delivery of molecules to eukaryotic cells is finding application in several disorders. This work introduces a new strategy for AD treatment based on the use of a Lactobacillus lactis strain carrying one plasmid (pExu) that contains a eukaryotic expression cassette encoding the human p62 protein. 3xTg-AD mice orally administered with these bacteria for two months showed an increased expression of endogenous p62 in the brain, with a protein delivery mechanism involving both lymphatic vessels and neural terminations, and positive effects on the major AD hallmarks. Mice showed ameliorated memory, modulation of the ubiquitin-proteasome system and autophagy, reduced levels of amyloid peptides, and diminished neuronal oxidative and inflammatory processes. Globally, we demonstrate that these extremely safe, non-pathogenic and non-invasive bacteria used as delivery vehicles for the p62 protein represent an innovative and realistic therapeutic approach in AD.

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Biosensors are versatile tools for monitoring molecular interactions. Herein, we report a novel assay designed to detect anti-platelet-derived growth factor receptor α (PDGFRα) autoantibodies in the serum of patients affected by systemic sclerosis (SSc), an autoimmune disease of the connective tissue. The assay was based on resonant mirror sensing, and used recombinant PDGFRα as molecular "bait" for anti-PDGFRα autoantibodies (IgG class). The selection and optimization of the analytical procedure required a preliminary investigation on the preservation of the native-like conformation of the receptor following the immobilization procedure. The PDGFRα-based biosensor was used to test IgG purified from sera of SSc patients and healthy controls (HC). The specificity and the reversibility of the interaction permitted a rapid analysis, a single detection test requiring only a few minutes. Remarkably, this assay could discriminate between SSc patients and HC. This receptor-based biosensor, based on the reversible interaction between a blocked macromolecule and soluble ligands, and with major advantages such as the rapidity, the reusability of the capturing surface and the low cost per single test, could represent a promising approach for the diagnosis of SSc and other diseases characterized by anti-receptor autoantibodies or other bioactive ligands to cellular receptors.

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