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Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g., might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, this new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions. Keywords: mitochondrial dysfunction, alzheimer’s disease, aging, oxidative stress, piracetam
Recent clinical data support the clinical use of oral lavender oil in patients suffering from subsyndromal anxiety. We identified the molecular mechanism of action that will alter the perception of lavender oil as a nonspecific ingredient of aromatherapy to a potent anxiolytic inhibiting voltage dependent calcium channels (VOCCs) as highly selective drug target. In contrast to previous publications where exorbitant high concentrations were used, the effects of lavender oil in behavioral, biochemical, and electrophysiological experiments were investigated in physiological concentrations in the nanomolar range, which correlate to a single dosage of 80 mg/d in humans that was used in clinical trials. We show for the first time that lavender oil bears some similarities with the established anxiolytic pregabalin. Lavender oil inhibits VOCCs in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines in the same range such as pregabalin. Interestingly, Silexan does not primarily bind to P/Q type calcium channels such as pregabalin and does not interact with the binding site of pregabalin, the α2δ subunit of VOCCs. Lavender oil reduces non-selectively the calcium influx through several different types of VOCCs such as the N-type, P/Q-type and T-type VOCCs. In the hippocampus, one brain region important for anxiety disorders, we show that inhibition by lavender oil is mainly mediated via N-type and P/Q-type VOCCs. Taken together, we provide a pharmacological and molecular rationale for the clinical use of the oral application of lavender oil in patients suffering from anxiety.
Typische neuropathologische Befunde bei der Alzheimer-Demenz (AD) sind die Bildung von Beta-Amyloid-Plaques, die Akkumulation von intrazellulären neurofibrillären Bündeln (Tangles) und ein ausgeprägter Verlust der Nervenzellen im Gehirn (siehe Estifanos Ghebremedhin und Thomas Deller »Risikofaktoren der Alzheimer-Krankheit. Was verraten uns die Gene?«, Seite 90). Insbesondere die Anhäufung von Beta-Amyloid-Peptid (Aß) scheint eine zentrale Rolle in der in der in der Pathogenese zu spielen und kausal für den Zelluntergang verantwortlich zu sein. Befunde unserer Arbeitsgruppe deuten darauf hin, das Aß zu mitochondrialer Dysfunktion in den Nervenzellen führt. Wir untersuchen die Kaskade der Mechanismen, die von der Bildung von Aß über mitochondriale Dysfunktion letztlich zu Synapsenverlust und Zelltod führen, mithilfe von Zelllinien und Mäusestämmen mit Alzheimer-typischen Merkmalen. Ziel ist, einen Angriffspunkt für die medikamentöse Behandlung der Alzheimer-Demenz zu finden. Als vielversprechend hat sich die Wirkung von Statinen erwiesen, die als Cholesterinhemmer eingesetzt werden. ...
Psoriasis is a characteristic inflammatory and scaly skin condition with typical histopathological features including increased proliferation and hampered differentiation of keratinocytes. The activation of innate and adaptive inflammatory cellular immune responses is considered to be the main trigger factor of the epidermal changes in psoriatic skin. However, the molecular players that are involved in enhanced proliferation and impaired differentiation of psoriatic keratinocytes are only partly understood. One important factor that regulates differentiation on the cellular level is Ca2+. In normal epidermis, a Ca2+ gradient exists that is disturbed in psoriatic plaques, favoring impaired keratinocyte proliferation. Several TRPC channels such as TRPC1, TRPC4, or TRPC6 are key proteins in the regulation of high [Ca2+]ex induced differentiation. Here, we investigated if TRPC channel function is impaired in psoriasis using calcium imaging, RT-PCR, western blot analysis and immunohistochemical staining of skin biopsies. We demonstrated substantial defects in Ca2+ influx in psoriatic keratinocytes in response to high extracellular Ca2+ levels, associated with a downregulation of all TRPC channels investigated, including TRPC6 channels. As TRPC6 channel activation can partially overcome this Ca2+ entry defect, specific TRPC channel activators may be potential new drug candidates for the topical treatment of psoriasis.