The molecular basis of platelet biogenesis, activation, aggregation and implications in neurological disorders.

Platelets are anucleated blood constituents, vital for hemostasis and involved in the pathophysiology of several cardiovascular, neurovascular diseases as well as inflammatory processes and metastasis. Over the past few years, the molecular processes that regulate the function of platelets in hemostasis and thrombosis have emerged revealing platelets to be perhaps more complex than may have been expected. The most understood part of platelets is to respond to a blood vessel injury by altering shape, secreting granule contents, and aggregating. These responses, while advantageous for hemostasis, can become detrimental when they root ischemia or infarction. Only a few transcription and signaling factors involved in platelet biogenesis have been identified till date. Platelets encompass an astonishingly complete array of organelles and storage granules including mitochondria, lysosomes, alpha granules, dense granules, a dense tubular system (analogous to the endoplasmic reticulum of nucleated cells); a highly invaginated plasma membrane system known as the open canalicular system (OCS) and large fields of glycogen. Platelets as a model cells to study neurological disorders have been recommended by several researchers since several counterparts exist between platelets and the brain, which make them interesting for studying the neurobiology of various neurological disorders. This review has been compiled with an aim to integrate the latest research on platelet biogenesis, activation and aggregation focusing on the molecular pathways that power and regulate these processes. The dysregulation of important molecular players affecting fluctuating platelet biology and thereby resulting in neurovascular diseases has also been discussed.

ACE-Triggered Hypertension Incites Stroke: Genetic, Molecular, and Therapeutic Aspects.

Stroke is the second largest cause of death worldwide. Angiotensin converting enzyme (ACE) gene has emerged as an important player in the pathogenesis of hypertension and consequently stroke. It encodes ACE enzyme that converts the inactive decapeptide angiotensin I to active octapeptide, angiotensin II (Ang II). Dysregulation in the expression of ACE gene, on account of genetic variants or regulation by miRNAs, alters the levels of ACE in the circulation. Variable expression of ACE affects the levels of Ang II. Ang II acts through different signal transduction pathways via various tyrosine kinases (receptor/non-receptor) and protein serine/threonine kinases, initiating a downstream cascade of molecular events. In turn these activated molecular pathways might lead to hypertension and inflammation thereby resulting in cardiovascular and cerebrovascular diseases including stroke. In order to regulate the overexpression of ACE, many ACE inhibitors and blockers have been developed, some of which are still under clinical trials.