Background: Migraine is a complex, chronic, painful, neurovascular disorder characterized by episodic activation of the trigeminal system. Increased levels of calcitonin gene-related peptide (CGRP) are found at different levels during migraine attacks. Interestingly, CGRP is also released within the trigeminal ganglia suggesting possible local effects on satellite cells, a specialized type of glia that ensheaths trigeminal neurons. CGRP was shown to enhance satellite-cell production of interleukin 1β (IL-1β), while trigeminal neurons express an activity-dependent production of nitric oxide (NO). Thus, in the present study we tested the hypothesis that IL-1β and NO induce trigeminal satellite cell activation, and that once activated these cells can influence neuronal responses.

The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second-generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24-week randomized, placebo-controlled, double-blind study. Patients aged 50-80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini-Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients' conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages.

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin corpus callosum, developmental delay, intellectual disability, seizures, optic atrophy, and spastic quadriplegia. Molecular dynamics simulations predicted long-range and/or local structural perturbations associated with the disease-causing mutations. Biochemical analyses documented variably reduced levels of TBCD, indicating relative instability of mutant proteins, and defective β-tubulin binding in a subset of the tested mutants. Reduced or defective TBCD function resulted in decreased soluble α/β-tubulin levels and accelerated microtubule polymerization in fibroblasts from affected subjects, demonstrating an overall shift toward a more rapidly growing and stable microtubule population. These cells displayed an aberrant mitotic spindle with disorganized, tangle-shaped microtubules and reduced aster formation, which however did not alter appreciably the rate of cell proliferation. Our findings establish that defective TBCD function underlies a recognizable encephalopathy and drives accelerated microtubule polymerization and enhanced microtubule stability, underscoring an additional cause of altered microtubule dynamics with impact on neuronal function and survival in the developing brain.

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