Elevated galanin may predict the risk of type 2 diabetes mellitus for development of Alzheimer’s disease

Zhang, Zhenwen; Fang, Penghua; Shi, Mingyi; Zhu, Yichao; Bo, Ping

doi:10.1016/j.mad.2015.08.001

Cited by 9 publications

(5 citation statements)

References 94 publications

(149 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Type 2 diabetes mellitus (T2DM) is a common, complex, and progressive metabolic disease, which is characterized by 3 pathophysiologic anomalies: relative insulin deficiency, insulin resistance, and hepatic insulin resistance (resulting in increased gluconeogenesis and impaired glycogen synthesis) ( 1 , 2 ). Importantly, the disease can lead to end-organ impairments in almost all vital organs, including the brain.…”

Section: Introductionmentioning

confidence: 99%

Metformin – a Future Therapy for Neurodegenerative Diseases

et al. 2017

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer’s disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties. Recently, scientists have put their efforts in establishing metformin’s role in the treatment of neurodegenerative diseases, such as AD, amnestic mild cognitive impairment and Parkinson’s disease. Results of several clinical studies confirm that long term use of metformin in diabetic patients contributes to better cognitive function, compared to participants using other anti-diabetic drugs. The exact mechanism of metformin’s advantageous activity in AD is not fully understood, but scientists claim that activation of AMPK-dependent pathways in human neural stem cells might be responsible for the neuroprotective activity of metformin. Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Aβ (β-amyloid). Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase (AChE), which is responsible for the degradation of acetylcholine (Ach), a neurotransmitter involved in the process of learning and memory. In regard to the beneficial effects of metformin, its anti-inflammatory and anti-oxidative properties cannot be omitted. Numerous in vitro and in vivo studies have confirmed that metformin ameliorates oxidative damage.

show abstract

Section: Introductionmentioning

confidence: 99%

Metformin – a Future Therapy for Neurodegenerative Diseases

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Type 2 diabetes mellitus (T2DM) is a complex, chronic, and progressive metabolic disease characterized by relative insulin deficiency, insulin resistance (primarily in fat, liver, and muscle cells), and high glucose levels in blood [1, 2]. Importantly, the disease can lead to severe impairments in almost all vital organs, including the brain.…”

Section: Introductionmentioning

confidence: 99%

Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

Markowicz-Piasecka

Sikora

Mateusiak

et al. 2017

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer's disease (AD). The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC50 = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL). Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.

show abstract

“…The widespread expression and physiologic functions of galanin in the central and peripheral nervous systems, and in tissues, such as the gastrointestinal tract and pancreas, demonstrate its importance and versatility for neuro-hormonal homeostasis ( 50 ). Galanin has been suggested to play significant roles in the neuroendocrine axis ( 9 , 10 , 51 ) for the mediation of diverse neuronal pathological conditions of ageing ( 51 , 52 ), feeding and energy metabolism ( 28 , 53 ), pancreatic secretion of insulin and diabetes ( 54 , 55 ), mood and behaviour ( 56 , 57 ), seizure ( 13 , 36 ), pain experience ( 53 ), bone density ( 58 ), cartilage growth plate physiology and repair ( 59 ) and skin ( 60 ).…”

Section: The Role Of Galanin Galp and Alarin In The Neuroendocrine Axismentioning

confidence: 99%

“…In the endocrine system, galanin was able to inhibit glucose-induced insulin release ( 61 – 63 ), by suppressing glucose-induced insulin secretion from rat islet cells ( 63 ). Accordingly, galanin has been implicated in regulating glucose metabolism, by improving insulin resistance and diabetes mellitus type 2 ( 54 , 64 ).…”

Section: The Role Of Galanin Galp and Alarin In The Neuroendocrine Axismentioning

confidence: 99%

Galanin family peptides: Molecular structure, expression and roles in the neuroendocrine axis and in the spinal cord

Zhu

Bennett

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

Galanin is a neurohormone as well as a neurotransmitter and plays versatile physiological roles for the neuroendocrine axis, such as regulating food intake, insulin level and somatostatin release. It is expressed in the central nervous system, including hypothalamus, pituitary, and the spinal cord, and colocalises with other neuronal peptides within neurons. Structural analyses reveal that the human galanin precursor is 104 amino acid (aa) residues in length, consisting of a mature galanin peptide (aa 33-62), and galanin message-associated peptide (GMAP; aa 63-104) at the C-terminus. GMAP appears to exhibit distinctive biological effects on anti-fungal activity and the spinal flexor reflex. Galanin-like peptide (GALP) has a similar structure to galanin and acts as a hypothalamic neuropeptide to mediate metabolism and reproduction, food intake, and body weight. Alarin, a differentially spliced variant of GALP, is specifically involved in vasoactive effect in the skin and ganglionic differentiation in neuroblastic tumors. Dysregulation of galanin, GALP and alarin has been implicated in various neuroendocrine conditions such as nociception, Alzheimer’s disease, seizures, eating disorders, alcoholism, diabetes, and spinal cord conditions. Further delineation of the common and distinctive effects and mechanisms of various types of galanin family proteins could facilitate the design of therapeutic approaches for neuroendocrine diseases and spinal cord injury.

show abstract

Elevated galanin may predict the risk of type 2 diabetes mellitus for development of Alzheimer’s disease

Cited by 9 publications

References 94 publications

Metformin – a Future Therapy for Neurodegenerative Diseases

Metformin – a Future Therapy for Neurodegenerative Diseases

Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

Galanin family peptides: Molecular structure, expression and roles in the neuroendocrine axis and in the spinal cord

Contact Info

Product

Resources

About