Activity-dependent neuroprotective protein (ADNP) is essential for brain formation and partial deficiency in ADNP results in cognitive deficits coupled with tauopathy and neuronal cell death. Our previous results indicated that a peptide snippet from ADNP, NAPVSIPQ (NAP, generic name, davunetide) can restore in part ADNP deficiencies. NAP interacts with tubulin and this interaction is displaced by the NAP related peptide that is derived from activity-dependent neurotrophic factor (ADNF), SALLRSIPA (SAL) and its all D-amino acid peptide derivative (D-SAL, also known as AL-309). Both NAP and D-SAL were shown to protect neurons against amyloid beta toxicity however the mechanism of protection is still under investigation. In addition, NAP protects against tau hyperphosphorylation associated with ADNP deficiency, in vivo. To investigate whether the mechanism of in vitro neuroprotection relates to the in vivo protection against tauopathy and to draw potential additional parallelism between NAP and D-SAL, we asked if: 1]NAP and D-SAL protect against amyloid beta related tau hyperphosphorylation in vitro; and 2] D-SAL protects against haploinsufficiency in ADNP, inhibiting tauopathy in vivo. Assessment of NAP and D-SAL neuroprotection in primary cortical neuro-glial cultures treated with amyloid beta showed that both peptides reduced toxin-related neuronal damage and protected against tau hyperphosphorylation. In vivo, chronic D-SAL administration protected against tau hyperphosphorylation associated with ADNP deficiency (ADNP+/- mice), showing for the first time protection against deficits in odor discrimination and in social recognition. These studies associate neuroprotection in vivo and in vitro and provide a broad base for future drug development based on NAP and D-SAL against multiple neurodegenerative conditions.
Invasive fungal diseases are increasingly important opportunistic infections that are intimately linked to immune-suppression in the context of cytotoxic treatment of neoplastic diseases, stem cell and solid-organ transplantation, and primary immune deficiencies. Mortality rates remain high despite the availability of novel antifungals that are both safe and highly active in vitro, suggesting that clinical outcomes may be improved through modulation of host immunity. Ongoing advances in our knowledge of fungal-host interactions facilitate rational design of novel immunotherapeutics. Thus, antifungal immunotherapy now includes age-old interventions such as granulocyte and immunoglobulin transfusions, as well as promising experimental techniques such as antifungal vaccines and adoptive immunotherapy. To realize the potential of these rapidly evolving technologies, transition from the bench to clinical-phase studies must occur at a more rapid pace.
Anti-phospholipid syndrome is an autoimmune disorder characterized by anti-phospholipid antibodies, arterial and venous thrombosis, pregnancy morbidity, and various neurological manifestations including psychiatric disorders. Higher incidence of various autoimmune disorders was found in schizophrenia. In addition, an association between the presence of anti-phospholipid antibodies and schizophrenia or psychosis was previously described, mainly as case reports. Although initially believed to be a result of neuroleptic treatment, the reasons for this association remain obscure. Several theories on the etiologic basis of schizophrenia that may explain this association were proposed including an immune basis of schizophrenia and a genetic locus of the disease in the human leukocyte antigens area. Herein, we present a series of five patients diagnosed with both schizophrenia and anti-phospholipid syndrome and their characteristics along with a comprehensive review of the current available literature on the subject in an attempt to deepen our understanding of these disorders and their pathogenesis.
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