Alzheimer Disease and Type 2 Diabetes Mellitus: The Link to Tyrosine Hydroxylase and Probable Nutritional Strategies

Abstract

Alzheimer disease (AD) and type 2 diabetes mellitus (T2DM) are chronic health disorders that affect millions of people around the world. According to recent studies, there are molecular similarities in the inflammatory pathways involved in both AD and T2DM, which opens a new avenue for researchers with different perspectives to target the cause of these diseases rather than their obvious symptoms. Several links between inflammation, cardiovascular disease, T2DM and central nervous system disorders such as AD and Parkinson's disease have been elucidated. Mutations in the hippocampal-β-amyloid precursor protein gene in genetically high-risk individuals have been shown to cause the early onset of AD symptoms. The overexpression of β-amyloid protein in the hippocampal region and the synaptotoxicity that occurs as a result have been considered a typical feature of AD and leads to neuronal loss and cognitive decline. However, the identity of the cellular components that cause the late onset of the disease seen in the majority of the cases is still unknown. Synaptic insults associated with neuronal dysfunction may involve several cascades and molecules, one of which has been hypothesized to be tyrosine hydroxylase (TH). The axons of the noradrenergic cells that project to the hippocampus appear to be affected by the β-amyloid protein, which subsequently contributes to TH loss in Alzheimer brain cells. In this review, we attempt to shed light on the important mechanisms involved in AD as well as T2DM such as inflammatory factors, abnormalities in the insulin signaling system and the possible role of the endocrine enzyme TH.

Dissecting the Potential Roles of Nigella sativa and Its Constituent Thymoquinone on the Prevention and on the Progression of Alzheimer's Disease

“…A possible role of the brain insulin resistance and a reduced insulin signaling in the AD's pathogenesis, was also described by several studies (Aliev et al, 2014 ). Baalba et al, by using streptozotocin-induced diabetic (STZ-T2DM) rats, showed that the daily intake of NSO induced the expression of insulin receptor and altered the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase (Balbaa et al, 2016 ).…”

Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs

“…The brain insulin resistance may be due to peripheral insulin resistance, reduced insulin uptake by brain and elevated brain Aβ deposition [9]. Several studies investigated the role of insulin resistance and impaired insulin signaling in the AD pathogenesis in brain [10] and neuro-inflammation is mutual interaction between T2DM and AD [11]. Chronic inflammation in T2DM and the leaking of peripheral inflammatory mediators from T2DM to brain induces microglial activation and release of the inflammatory mediators IL-1β, IL-6 and TNF-α in brain [12].…”

Catecholamines in Alzheimer's Disease: A Systematic Review and Meta-Analysis

“…To date, a number of factors have been proposed to cause age-induced damage to the brain, including oxidative stress, free radical damage, and intracellular fibrillary tangles, which can be modified by aging, and have been associated with occurrence of AD (Mohsenzadegan and Mirshafiey, 2012 ; Tatsumi et al, 2014 ). Moreover, DA deficiency was found to contribute to age-related changes (Aliev et al, 2014 ). Meanwhile, previous research showed that DA density progressively reduced with aging and more severely in cases with AD (Rieckmann et al, 2018 ).…”