DPP-4 inhibitors and type 2 diabetes mellitus in Parkinson’s disease: a mutual relationship

Alrouji, Mohammed; Al-Kuraishy, Hayder M; Al-Buhadily, Ali K; Al-Gareeb, Ali I; Elekhnawy, Engy; Batiha, Gaber El‐Saber

doi:10.1007/s43440-023-00500-5

Cited by 12 publications

(10 citation statements)

References 82 publications

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“…NEP inhibition by specific inhibitors augments circulating GLP‐1, which has a neuroprotective effect against Aβ‐induced cytotoxicity, neuroinflammation, synaptic dysfunction‐induced memory and cognitive dysfunctions 82 . Long 84 ‐acting GLP‐1 analogues are highly resistant to the effect of DPP4 85 . Notably, long‐acting GLP‐1 analogues are mainly degraded by NEP, whereas endogenous GLP‐1 is mainly degraded by DPP4 85 .…”

Section: Mechanistic Role Of Nep Inhibitors In Admentioning

confidence: 99%

“…A prospective study involving 253 T2DM patients on sitagliptin or non‐sitagliptin treatments illustrated that DPP4 inhibitor sitagliptin improved cognitive function compared to other diabetic therapies 91 . The cognitive enhancement effect of DPP4 inhibitors is related to the augmentation of GLP‐1 84 . Despite the risk of Aβ accumulation in NEP‐deficient mice, they experience less cognitive dysfunction due to the high concentration of GLP‐1 in the brain 92 .…”

Section: Mechanistic Role Of Nep Inhibitors In Admentioning

confidence: 99%

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Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2023

J Cellular Molecular Medi

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Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aβ). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aβ. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aβ and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aβ. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aβ clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon‐like peptide 1 (GLP‐1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP‐1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.

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Section: Mechanistic Role Of Nep Inhibitors In Admentioning

confidence: 99%

Section: Mechanistic Role Of Nep Inhibitors In Admentioning

confidence: 99%

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2023

J Cellular Molecular Medi

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“…19 Furthermore, the frequency of Parkinson's disease is higher in Western countries in comparison with the Asian population. 20 The neuropathology of Parkinson's disease (PD) arises from the gradual deterioration of dopaminergic neurons located in the substantia nigra, as well as the build-up of Lewy bodies within the survival motor neurons. 21 The primary cause of Lewy bodies is the deposition of α-Syn, which is also present in other neurological conditions known as synucleinopathies.…”

Section: Pathog Ene S Is and Clini C Al Fe Ature Of Pdmentioning

confidence: 99%

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy

Ali,

Al‐Kuraishy,

Al‐Gareeb

et al. 2024

J Cellular Molecular Medi

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Parkinson's disease (PD) is a neurodegenerative disorder of the brain and is manifested by motor and non‐motor symptoms because of degenerative changes in dopaminergic neurons of the substantia nigra. PD neuropathology is associated with mitochondrial dysfunction, oxidative damage and apoptosis. Thus, the modulation of mitochondrial dysfunction, oxidative damage and apoptosis by growth factors could be a novel boulevard in the management of PD. Brain‐derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase type B (TrkB) are chiefly involved in PD neuropathology. BDNF promotes the survival of dopaminergic neurons in the substantia nigra and enhances the functional activity of striatal neurons. Deficiency of the TrkB receptor triggers degeneration of dopaminergic neurons and accumulation of α‐Syn in the substantia nigra. As well, BDNF/TrkB signalling is reduced in the early phase of PD neuropathology. Targeting of BDNF/TrkB signalling by specific activators may attenuate PD neuropathology. Thus, this review aimed to discuss the potential role of BDNF/TrkB activators against PD. In conclusion, BDNF/TrkB signalling is decreased in PD and linked with disease severity and long‐term complications. Activation of BDNF/TrkB by specific activators may attenuate PD neuropathology.

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“…GABA pathway plays a critical role in regulating inhibitory tone on the globus pallidus (GP), SNpc, and thalamus, preventing excessive stimulation of the cerebral cortex [ 43 ]. Dysregulation of the GABA pathway in PD triggers neuronal hyper-excitability, leading to dyskinesia or bradykinesia [ 43 , 44 ]. Deregulation of the GABA pathway may be involved in developing and progressing motor and non-motor manifestations in PD [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit

Alharbi,

Al-kuraishy,

Al-Gareeb

et al. 2024

Eur J Med Res

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Parkinson's disease (PD) is a progressive neurodegenerative disease as a result of the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental features of PD are motor and non-motor symptoms. PD symptoms develop due to the disruption of dopaminergic neurotransmitters and other neurotransmitters such as γ-aminobutyric acid (GABA). The potential role of GABA in PD neuropathology concerning the motor and non-motor symptoms of PD was not precisely discussed. Therefore, this review intended to illustrate the possible role of GABA in PD neuropathology regarding motor and non-motor symptoms. The GABA pathway is essential in regulating the inhibitory tone to prevent excessive stimulation of the cerebral cortex. Degeneration of dopaminergic neurons in PD is linked with reducing GABAergic neurotransmission. Decreasing GABA activity promotes mitochondrial dysfunction and oxidative stress, which are highly related to PD neuropathology. Hence, restoring GABA activity by GABA agonists may attenuate the progression of PD motor symptoms. Therefore, dysregulation of GABAergic neurons in the SNpc contributes to developing PD motor symptoms. Besides, PD non-motor symptoms are also related to the dysfunction of the GABAergic pathway, and amelioration of this pathway may reduce PD non-motor symptoms. In conclusion, the deregulation of the GABAergic pathway in PD might be intricate in developing motor and non-motor symptoms. Improving this pathway might be a novel, beneficial approach to control PD symptoms.

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DPP-4 inhibitors and type 2 diabetes mellitus in Parkinson’s disease: a mutual relationship

Cited by 12 publications

References 82 publications

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy

Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit

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