Corrigendum: Human Cerebral Cortex Proteome of Fragile X-Associated Tremor/Ataxia Syndrome.

[This corrects the article DOI: 10.3389/fmolb.2020.600840.].

Human Cerebral Cortex Proteome of Fragile X-Associated Tremor/Ataxia Syndrome.

Background: Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder associated with premutation CGG-repeat expansions (55-200 repeats) in the 5' non-coding portion of the fragile X mental retardation 1 (FMR1) gene. Core features of FXTAS include progressive tremor/ataxia, cognitive decline, variable brain volume loss, and white matter disease. The principal histopathological feature of FXTAS is the presence of central nervous system (CNS) and non-CNS intranuclear inclusions. Objective: To further elucidate the molecular underpinnings of FXTAS through the proteomic characterization of human FXTAS cortexes. Results: Proteomic analysis of FXTAS brain cortical tissue (n = 8) identified minor differences in protein abundance compared to control brains (n = 6). Significant differences in FXTAS relative to control brain predominantly involved decreased abundance of proteins, with the greatest decreases observed for tenascin-C (TNC), cluster of differentiation 38 (CD38), and phosphoserine aminotransferase 1 (PSAT1); proteins typically increased in other neurodegenerative diseases. Proteins with the greatest increased abundance include potentially novel neurodegeneration-related proteins and small ubiquitin-like modifier 1/2 (SUMO1/2). The FMRpolyG peptide, proposed in models of FXTAS pathogenesis but only identified in trace amounts in the earlier study of FXTAS inclusions, was not identified in any of the FXTAS or control brains in the current study. Discussion: The observed proteomic shifts, while generally relatively modest, do show a bias toward decreased protein abundance with FXTAS. Such shifts in protein abundance also suggest altered RNA binding as well as loss of cell-cell adhesion/structural integrity. Unlike other neurodegenerative diseases, the proteome of end-stage FXTAS does not suggest a strong inflammation-mediated degenerative response.

An orally active immune adjuvant prepared from cones of Pinus sylvestris, enhances the proliferative phase of a primary T cell response.

BACKGROUND: We have previously demonstrated that an alkaline extract of shredded pinecones yields a polyphenylpropanoid polysaccharide complex (PPC) that functions as an orally active immune adjuvant. Specifically, oral PPC can boost the number of antigen-specific memory CD8+ T cells generated in response to a variety of vaccine types (DNA, protein, and dendritic cell) and bias the response towards one that is predominately a T helper 1 type. METHODS: An immune response was initiated by intraperitoneal injection of mice with Staphylococcus enterotoxin B (SEB). A group of mice received PPC by gavage three times per day on Days 0 and 1. The draining lymph nodes were analyzed 48-96 h post-injection for the numbers of reactive T cells, cytokine production, the generation of reactive oxygen species, and apoptotsis. RESULTS: In this study we examined whether the ability of PPC to boost a T cell response is due to an effect on the proliferative or contraction phases, or both, of the primary response. We present data to demonstrate that oral PPC significantly enhances the primary T cell response by affecting the expansion of T cells (both CD4 and CD8) during the proliferative phase, while having no apparent effects on the activation-induced cell death associated with the contraction phase. CONCLUSIONS: These findings suggest that PPC could potentially be utilized to enhance the T cell response generated by a variety of prophylactic and therapeutic vaccines designed to target a cellular response.