The Pharmacological Activity of Garlic (Allium sativum) in Parkinson's Disease: From Molecular Mechanisms to the Therapeutic Potential.

Parkinson's disease (PD), one of the most common neurological diseases worldwide, is mainly characterized neuropathologically by the dopaminergic neurodegeneration in the substantia nigra pars compacta of the brainstem. Genetic and environmental factors contribute to PD pathophysiology through modulation of pleiotropic cellular mechanisms. The currently available treatment options focus only on replenishing dopamine and do not alter disease progression. Interestingly, garlic (Allium sativum), globally famed for its flavor and taste-enhancing properties, has shown protective activity in different PD models. Numerous chemical constituents of garlic, mainly the organosulfur compounds, have been shown to exhibit anti-Parkinsonian effects by targeting oxidative stress, mitochondrial impairment, and neuroinflammation-related signaling. However, despite its therapeutic potential against PD, the major bioactive components of garlic display some stability issues and some adverse effects. In the present review, we explore the therapeutic potential of garlic and its major constituents in PD, the molecular mechanisms responsible for its pharmaceutical activity, and the associated limitations that need to be overcome for its future potential use in clinical practice.

Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.