Alzheimer's disease (AD) is one of the most prominent neurodegenerative diseases, which impairs cognitive function in afflicted individuals. AD results in gradual decay of neuronal function as a consequence of diverse degenerating events. Several neuroimmune players (such as cytokines and growth factors that are key players in maintaining CNS homeostasis) turn aberrant during crosstalk between the innate and adaptive immunities. This aberrance underlies neuroinflammation and drives neuronal cells toward apoptotic decline. Neuroinflammation involves microglial activation and has been shown to exacerbate AD. This review attempted to elucidate the role of cytokines, growth factors, and associated mechanisms implicated in the course of AD, especially with neuroinflammation. We also evaluated the propensities and specific mechanism(s) of cytokines and growth factors impacting neuron upon apoptotic decline and further shed light on the availability and accessibility of cytokines across the blood-brain barrier and choroid plexus in AD pathophysiology. The pathogenic and the protective roles of macrophage migration and inhibitory factors, neurotrophic factors, hematopoietic-related growth factors, TAU phosphorylation, advanced glycation end products, complement system, and glial cells in AD and neuropsychiatric pathology were also discussed. Taken together, the emerging roles of these factors in AD pathology emphasize the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

Alzheimer's disease (AD) is the most common type of dementia and progressive neurodegenerative disease. The presence of β‐amyloid (Aβ) plaques and phosphorylated Tau tangles are considered to be the two main hallmarks of AD. Recent findings have shown that different changes in the structure and dynamics of mitochondria play an important role in AD pathology progression. Mitochondrial changes in AD are expressed as enhanced mitochondrial fragmentation, altered mitochondrial dynamics, and changes in the expression of mitochondrial biogenesis genes in vitro and in vivo models. Therefore, targeting mitochondria and associated mitochondrial proteins seems to be a promising alternative instead of targeting Aβ and Tau in the prevention of Alzheimer's disease. The dynamin‐related protein (Drp1) is one such protein that plays an important role in the regulation of mitochondrial division and maintenance of mitochondrial structures. Few researchers have shown that inhibition of Drp1 GTPase activity in neuronal cells rescues excessive mitochondrial fragmentation. In addition, the growing evidence revealed that Drp1 can interact with both Aβ and Tau protein in human brain tissues and mouse models. In this review, we would like to update existing knowledge about various changes in and around mitochondria related to the pathogenesis of Alzheimer's disease, with particular emphasis on mitophagy and autophagy.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized mainly by the gradual decay in neuronal function as a consequence of diverse degenerating events primarily including mitochondria dysfunction and cascades of neuro-immune reactions. Besides the acquired harmful reactive oxygen species (ROS), neurotoxins, and amyloid-beta (Aβ) and TAU pathologies in neurons, accumulating evidence with time underlined the roles of cytokines and growth factors in the AD pathogenesis. It may help us in evaluating the propensities and specific mechanism(s) of cytokines and factors impacting neuron upon apoptotic decline. Proinflammatory cytokines often induce inflammation in AD and AD-like pathogenesis in response to the apoptotic scenarios where some growth factors are involved in cytokinetic reactions to activate microglia and causing inflammation in AD. In this report, we comprehensively reviewed role of cytokines and chemokines in immune response to AD and neuropsychiatry. We provided insights into the neuroinflammation and the role of diverse factors including the pro-/anti-inflammatory cytokines, APP, TAU phosphorylation, glycation end products, complement system, and the role of glial cells. Also, we discussed the pathogenic and protective role of macrophage migration inhibitory factors, choroid plexus-, neurotrophic- and hematopoietic -related growth factors in AD. We further shed light on the availability and accessibility of the cytokines across the blood-brain barrier in AD pathophysiology. Taken together, the emerging role of these factors in AD pathology emphasized the importance of building novel strategies for an effective therapeutic/neuropsychiatric management of AD in clinics.

The purpose of our article is to assess the current understanding of Indian spice, curcumin, against amyloid-β (Aβ)-induced toxicity in Alzheimer's disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes, and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on Aβ and curcumin has revealed that curcumin prevents Aβ aggregation and crosses the blood-brain barrier, reach brain cells, and protect neurons from various toxic insults of aging and Aβ in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin's bioavailability and urgent need for new formulations to increase its brain levels to treat patients with AD.

The purpose of our study was to develop a therapeutic target that can reduce Aβ and Drp1 levels, and also can inhibit abnormal interactions between Aβ and Drp1 in AD neurons. To achieve this objective, we designed various compounds and their 3-dimensional molecular structures were introduced into Aβ and Drp1 complex and identified their inhibitory properties against Aβ-Drp1 interaction. Among all, DDQ was selected for further investigation because of 1) its best docking score and 2) its binding capability at interacting sites of Drp1 and Aβ complex. We synthesized DDQ using retro-synthesis and analyzed its structure spectrally. Using biochemical, molecular biology, immunostaining and transmission electron microscopy (TEM) methods, we studied DDQ's beneficial effects in AD neurons. We measured the levels of Aβ and Drp1, Aβ and Drp1 interaction, mRNA and protein levels of mitochondrial dynamics, biogenesis and synaptic genes, mitochondrial function and cell viability and mitochondrial number in DDQ-treated and untreated AD neurons. Our qRT-PCR and immunoblotting analysis revealed that reduced levels of mitochondrial fission and increased fusion, biogenesis and synaptic genes in DDQ-treated AD neurons. Our immunoblotting and immunostaining analyses revealed that Aβ and Drp1 levels were reduced in DDQ-treated AD neurons. Interaction between Aβ and Drp1 is reduced in DDQ-treated AD neurons. Aβ42 levels were significantly reduced in DDQ-treated mutant APPSwe/Ind cells. Mitochondrial number is significantly reduced and mitochondrial length is significantly increased. Mitochondrial function and cell viability were maintained in AD neurons treated with DDQ. These observations indicate that DDQ reduces excessive mitochondrial fragmentation, enhances fusion, biogenesis and synaptic activity and reduces Aβ42 levels and protects AD neurons against Aβ-induced mitochondrial and synaptic toxicities.

Previously we have demonstrated the beneficial effect of tocotrienol (TT, extracted from annatto consisting of 90% delta‐TT and 10% gamma‐TT) on glucose homeostasis in inbred male obese C57BL/6J mice. This study further examines the effects of TT in conjunction with statin on high‐fat‐diet‐(HFD)‐induced insulin resistance of obese outbred CD‐1 mice. In order to compare the effects of TT and statin and the interactive effects between these treatments, a 2 (no TT vs. TT) × 2 (no statin vs. statin) factorial ANOVA was used. Forty male CD‐1 mice (6‐weeks‐old) were assigned to 4 groups (n=10/group): HFD, HFD+TT (TT at 60 mg/kg body weight via oral feeding, 5x/week), HFD+statin (statin at 120 mg/kg diet), and HFD+TT+statin for 14 weeks. To determine the effects of TT and statin on glucose homeostasis and insulin resistance, glucose tolerance (GTT, 2g glucose/kg of body weight) and insulin tolerance (ITT, 1U/kg of body weight) tests were performed. The HFD group had impaired glucose tolerance and was insulin resistant as determined by GTT and ITT, respectively. Statin treatment alone improved the glucose homeostasis while TT alone had no beneficial effect. Interestingly, TT and statin had positive synergistic effect in improving glucose homeostasis. Both TT and statin treatment, alone or in combination, improved insulin sensitivity. Overall, our data demonstrates that TT and statin collectively improve glucose homeostasis and insulin sensitivity. Support or Funding Information American River Nutrition, Inc., Hadley, MA.