Galantamine-Memantine combination in the treatment of Alzheimer's disease and beyond

Koola, Maju Mathew

doi:10.1016/j.psychres.2020.113409

Cited by 49 publications

(41 citation statements)

References 141 publications

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“…Neuroinflammation in schizophrenia has been questioned (Birnbaum et al, 2018; Birnbaum & Weinberger, 2020; Kishimoto, Horigome, & Takamiya, 2018). KYNA‐centric pathophysiology as outlined above (Koola, 2020): KYNA levels bidirectionally modulate levels of dopamine, acetylcholine, glutamate, and GABA (Myint & Kim, 2014; Pocivavsek, Notarangelo, Wu, Bruno, & Schwarcz, 2016; Tanaka et al, 2020; Wonodi & Schwarcz, 2010) and redox‐neuroinflammatory systems (Ayala et al, 2015; Coyle and Puttfarcken, 1993; Kindler et al, in press; Lugo‐Huitrón et al, 2011; Pedraz‐Petrozzi, Elyamany, Rummel, & Mulert, 2020; D. O. Perkins, Jeffries, Do, 2020). Quintuple hypotheses target dopamine, nicotinergic‐cholinergic, glutamate/NMDA, GABA, and KYNA hypotheses simultaneously (Koola, 2018a).…”

Section: Why Did We Fail To Bend the Curve?mentioning

confidence: 99%

“…The combination treatment may improve positive, cognitive, and negative symptoms of schizophrenia (Koola, 2018a; Koola et al, 2019). Finally, the combination also may stabilize other major pathophysaiological mechanisms (including the KYNA‐centric pathophysiology [Koola, 2020]) and biomarkers as shown in Figures 1–3. There is burgeoning preclinical (Egea et al, 2007; Hodgkins & Schwarcz, 1998; Kety, 1959; Sobrado, Roda, López, Egea, & García, 2004) and clinical evidence on lactate as a biomarker in schizophrenia and beyond (Altschule, Henneman, Holliday, & Goncz, 1956; Regenold et al, 2009; Sullivan, et al, 2019).…”

Section: Potential Combination Treatments In Schizophreniamentioning

confidence: 99%

“…Nicotinic (Dwyer, McQuown, & Leslie, 2009) and NMDA receptors (Ben‐Ari, Khazipov, Leinekugel, Caillard, & Gaiarsa, 1997) are critically involved in neurodevelopment. There is considerable evidence on the interactive effects of α7nACh and NMDA receptors (Askew and Metherate, 2016; Bali et al, 2017, 2019a, 2019b; Elnagar et al, 2018; Hamilton et al, 2018; Jerusalinsky, Kornisiuk, & Izquierdo, 1997; Koola, 2020; Koukouli & Maskos, 2015; Levy & Aoki, 2002; Lin et al, 2010, 2014a, 2014b; Li, Nai, Lipina, Roder, & Liu, 2013; Lozada et al, 2012; Parikh, Ji, Decker, & Sarter, 2010; Phenis et al, 2020; Moriguchi, Marszalec, Zhao, Yeh, & Narahashi, 2004; Schilström, Ivanov, Wiker, & Svensson, 2007; Tang et al, 2018; Timofeeva & Levin, 2011; H. L. Wang et al, 2006; Y. Wang et al, 2015; Zhang, Li, Li, & Liu, 2016; Zhao et al, 2006). α7nAChR may protect against glutamate neurotoxicity and prevent cell death (J. P. Lopes, Tarozzo, Reggiani, Piomelli, & Cavalli., 2013; Shimohama et al, 1998, 2018).…”

Section: α7 Nicotinic‐nmda Hypothesis: Paradigm Shiftmentioning

confidence: 99%

“…KYNA is the next frontier for neuropsychiatric diseases; the KP was described as a finger in every pie recently (Crespie, 2019; Savitz, 2020). KYNA‐centric pathophysiology (Koola, 2020) may be of considerable value in the treatment of many neuropsychiatric diseases. Nicotinic and NMDA receptors seem to be the underlying mechanism of major symptoms and biomarkers in many neuropsychiatric diseases (Koola, 2018c; Koola et al, 2019) as shown in Figure 3.…”

Section: Schizophrenia and Beyondmentioning

confidence: 99%

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Alpha7 nicotinic‐N‐methyl‐D‐aspartate hypothesis in the treatment of schizophrenia and beyond

Koola

2020

Human Psychopharmacology

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Development of novel treatments for positive, cognitive, and negative symptoms continue to be a high‐priority area of schizophrenia research and a major unmet clinical need. Given that all randomized controlled trials (RCTs) conducted to date failed with one add‐on medication/mechanism of action, future RCTs with the same approach are not warranted. Even if the field develops a medication for cognition, others are still needed to treat negative and positive symptoms. Therefore, fixing one domain does not completely solve the problem. Also, targeting the cholinergic system, glutamatergic system, and cholinergic plus alpha7 nicotinic and N‐methyl‐D‐aspartate (NMDA) receptors failed independently. Hence, targeting other less important pathophysiological mechanisms/targets is unlikely to be successful. Meta‐analyses of RCTs targeting major pathophysiological mechanisms have found some efficacy signal in schizophrenia; thus, combination treatments with different mechanisms of action may enhance the efficacy signal. The objective of this article is to highlight the importance of conducting RCTs with novel combination treatments in schizophrenia to develop antischizophrenia treatments. Positive RCTs with novel combination treatments that target the alpha7 nicotinic and NMDA receptors simultaneously may lead to a disease‐modifying therapeutic armamentarium in schizophrenia. Novel combination treatments that concurrently improve the three domains of psychopathology and several prognostic and theranostic biomarkers may facilitate therapeutic discovery in schizophrenia.

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Section: Why Did We Fail To Bend the Curve?mentioning

confidence: 99%

Section: Potential Combination Treatments In Schizophreniamentioning

confidence: 99%

Section: α7 Nicotinic‐nmda Hypothesis: Paradigm Shiftmentioning

confidence: 99%

Section: Schizophrenia and Beyondmentioning

confidence: 99%

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Alpha7 nicotinic‐N‐methyl‐D‐aspartate hypothesis in the treatment of schizophrenia and beyond

Koola

2020

Human Psychopharmacology

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“…KYNA has antioxidant properties that scavenges ROS to suppress overshooting inflammation in damaging tissues. Reduced concentrations of KYNA may contribute to tissue damage and inflammatory cell proliferation neurodegenerative diseases [3,10,25,26]. In addition, KYNA was reported to contribute to weight reduction without affecting osteogenesis [27].…”

Section: Introductionmentioning

confidence: 99%

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

Török¹,

Maszlag-Török²,

Molnár³

et al. 2021

Preprint

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Aims Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3- dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) has been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. Main methods SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. Key findings No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. Significance The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

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Lipid‐Based Nanocarriers Enabled Oral Delivery of Oleanolic Acid Derivative DKS26 for Diabetes Management

Ban

Chu

Pan

et al. 2023

Adv Healthcare Materials

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Oleanolic acid derivative DKS26 has hypolipidemic, islet, and hepatoprotective effects. However, high lipophilicity and low water solubility led to DKS26 extremely low oral bioavailability. Herein, lipid-based nanocarriers, including lipid nanodiscs (sND/DKS26) and liposomes (sLip/DKS26), are prepared to improve DKS26 oral absorption. In comparison to free DKS26 (5.81%), the absolute oral bioavailabilities are significantly increased to 29.47% (sND/DKS26) and 37.25% (sLip/DKS26) without detectable toxicity or immunogenicity even after repeated administrations. Both sND/DKS26 and sLip/DKS26 significantly reduce the feeding glucose level and the AUC of OGTT in db/db diabetic mice. Aiding by the newly developed scFv-based nanocarrier separation methods, no intact nanocarriers are detected in blood circulation after oral administration, suggesting that both formulations are unable to penetrate the intestinal epithelium. They enhance DKS26 absorption mainly by improving intestinal cell uptake and rapid intracellular release of the payload. Since pre-existing anti-PEG is widely detected in humans, the present oral absorption pathway of both nanocarriers successfully avoids unfavorable immunological responses after interaction with anti-PEG antibodies. The application of lipid-based nanocarriers paves an efficient and safe avenue for the clinical translation and application of poorly soluble therapeutics derived from traditional Chinese medicine.

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Galantamine-Memantine combination in the treatment of Alzheimer's disease and beyond

Cited by 49 publications

References 141 publications

Alpha7 nicotinic‐N‐methyl‐D‐aspartate hypothesis in the treatment of schizophrenia and beyond

Alpha7 nicotinic‐N‐methyl‐D‐aspartate hypothesis in the treatment of schizophrenia and beyond

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

Lipid‐Based Nanocarriers Enabled Oral Delivery of Oleanolic Acid Derivative DKS26 for Diabetes Management

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