Tissue-Nonspecific Alkaline Phosphatase in Central Nervous System Health and Disease: A Focus on Brain Microvascular Endothelial Cells

Abstract

Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme bound to the plasma membranes of numerous cells via a glycosylphosphatidylinositol (GPI) moiety. TNAP’s function is well-recognized from earlier studies establishing its important role in bone mineralization. TNAP is also highly expressed in cerebral microvessels; however, its function in brain cerebral microvessels is poorly understood. In recent years, few studies have begun to delineate a role for TNAP in brain microvascular endothelial cells (BMECs)—a key component of cerebral microvessels. This review summarizes important information on the role of BMEC TNAP, and its implication in health and disease. Furthermore, we discuss current models and tools that may assist researchers in elucidating the function of TNAP in BMECs.

Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease

“…As the isozyme name “tissue-nonspecific” implies, TNALP is expressed ubiquitously and modified by post-translational glycosylation processes, to become isoforms that provide significant proteomic diversity and specificity relating to various tissues and cells. The highest levels of human TNALP isoforms are expressed in bone, liver, and kidney tissues [ 1 ]; with neutrophil granulocytes [ 5 ], brain [ 6 ], and vascular cells [ 7 ] as secondary sources of TNALP activity.…”

“…The underlying mechanisms may include a disturbance of vitamin B6 metabolism, since pyridoxal 5′-phosphate, the active form of vitamin B6, is an endogenous substrate for ALP and important for neuronal function in the brain [ 64 ]. In addition, ALP is also involved in cerebral neurotransmission [ 65 ] and contributes to the integrity of the blood–brain barrier [ 6 , 66 ]. While there may be a physiologic role for increased ALP in acute inflammatory states, e.g., sepsis, where increased ALP is associated with improved short-term outcome [ 67 , 68 ], elevated ALP in chronic disease is invariably associated with negative outcomes.…”

Relationship between serum alkaline phosphatase and poor 3-month prognosis in acute ischemic stroke patients with preserved renal function: results from Xi’an Stroke Registry Study of China

“…Apart from the different clinical characteristics from our included population, some previous basic investigations showed that low ALP levels could increase the amount of inhibitory pyrophosphate resulting in abnormal metabolism of pyridoxine-5 '-phosphate (the main form of vitamin B6) and hypomineralization of the skeleton. The loss of mineralization could cause a variety of symptoms including softening of bone, bowing and spontaneous breakage of bones, rickets and tooth defects [ 23 , 24 ]. However, whether the reduced ALP level could be associated with poor 3-month prognosis in AIS patient with preserved renal function needs to be further explored and verified by subsequent relevant basic experiments.…”

Evaluation of Diagnostic Role of Alkaline Phosphatase in the Patients of Cerebral Stroke

“…11 The TNAP protein is commonly found in bones, intestines, livers and brains. 23 As well as playing a role in inflammatory processes, ALP causes cerebral stroke, which is also an inflammatory injury to brain cells. 24 ALP deactivates ATP production, which is a dangerous signal for injury of cells.…”

“…11 TNAP is found in brain tissues and the nervous system. 12 In the brain, TNAP is responsible for the development of various tissues, such as the myelin sheath. Under the influence of TNAP, different neurotransmitters are synthesized and regulated.…”