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Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aβ pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neurodegenerative diseases (NDD) are incurable and the most prevalent cognitive and motor disorders of elderly. Mitochondria are essential for a wide range of cellular processes playing a pivotal role in a number of cellular functions like metabolism, intracellular signaling, apoptosis, and immunity. A plethora of evidence indicates the central role of mitochondrial functions in pathogenesis of many aging related NDD. Considering how mitochondria function in neurodegenerative diseases, oxidative stress, and mutations in mtDNA both contribute to aging. Many substantial reports suggested the involvement of numerous contributing factors including, mitochondrial dysfunction, oxidative stress, mitophagy, accumulation of somatic mtDNA mutations, compromised mitochondrial dynamics, and transport within axons in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Therapies therefore target fundamental mitochondrial processes such as energy metabolism, free-radical generation, mitochondrial biogenesis, mitochondrial redox state, mitochondrial dynamics, mitochondrial protein synthesis, mitochondrial quality control, and metabolism hold great promise to develop pharmacological based therapies in NDD. By emphasizing the most efficient pharmacological strategies to target dysfunction of mitochondria in the treatment of neurodegenerative diseases, this review serves the scientific community engaged in translational medical science by focusing on the establishment of novel, mitochondria-targeted treatment strategies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Parkinson's disease is a neurodegenerative disorder which is characterised mostly by loss of dopaminergic nerve cells throughout the nigral area mainly as a consequence of oxidative stress. Muscle stiffness, disorganised bodily responses, disturbed sleep, weariness, amnesia, and voice impairment are all symptoms of dopaminergic neuron degeneration and existing symptomatic treatments are important to arrest additional neuronal death. Some cannabinoids have recently been demonstrated as robust antioxidants that might protect the nerve cells from degeneration even when cannabinoid receptors are not triggered. Cannabinoids are likely to have property to slow or presumably cease the steady deterioration of the brain's dopaminergic systems, a condition for which there is now no treatment. The use of cannabinoids in combination with currently available drugs has the potential to introduce a radically new paradigm for treatment of Parkinson's disease, making it immensely useful in the treatment of such a debilitating illness., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease causes loss of memory and deterioration of mental abilities is utmost predominant neurodegenerative disease accounting 70-80% cases of dementia. The appearance of plaques of amyloid-β and neurofibrillary tangles in the brain post-mortems of Alzheimer's patients established them as key participants in the etiology of Alzheimer's disease. Exosomes exist as extracellular vesicles of nano-size which are present throughout the body. Exosomes are known to spread toxic hyperphosphorylated tau and amyloid-β between the cells and are linked to the loss of neurons by inducing apoptosis. Exosomes have progressed from cell trashcans to multifunctional organelles which are involved in various functions like internalisation and transmission of macromolecules such as lipids, proteins, and nucleic acids. This review covers current findings on relationship of exosomes in biogenesis and angiogenesis of Alzheimer's disease and functions of exosomes in the etiology of AD. Furthermore, the roles of exosomes in development, diagnosis, treatment, and its importance as therapeutic targets and biomarkers for Alzheimer's disease have also been highlighted., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Antidepressant use has resulted in a variety of negative consequences, including permanent brain damage and erectile dysfunction. So, the purpose lies in developing something more productive with minimal side effects and consequently improved efficacy. A growing body of evidences indicated a remarkable purinergic signalling system, which helped in dealing with this complication. This has been found to be a powerful formula in dealing with psychiatric disorders. P1 (adenosine), P2X, and P2Y (ATP) are the receptors, involved in the pathology as well as exhibiting the therapeutic action by triggering the purinergic pathway. It was found that A2A and P2X7 receptors specifically were involved and recognized as possible targets for treating depression. Further, the development of biomarkers for the diagnosis of depression has also been attributed to accelerate the process. One such biomarker includes serum uric acid. Many clinical studies reveal the importance of antagonizing P2X7 and A2A receptors, for promising research in understanding the molecular premises of depression. However, further investigations are still needed to be done to open several unfolded mysteries for a better and safe upshot. The selective antagonists for A2A and P2X7 receptors may have antidepressant effects showing positive results, in agreement with non-clinical testing. In this review, efforts are being devoted to the targeted receptors in bringing out antidepressant effects with a possible link involving depression and defined purinergic signalling. Additionally, the overview of various receptors, including their functions and distribution, is being explored in a representative way along with the biomarkers involved., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The degradation of neurons marks as the pathological reason for onset of most of the neurological diseases although the functional deficiencies and symptoms may vary. Insulin-like growth factor-I (IGF-I) boosts regeneration of both motor and sensory neurons and thus presents as a potential treatment in management of neurological disorders. IGF-I is a pleiotropic agent which stimulates the survival and outgrowth of neurons accompanied by their motility as well as myelination by glial cells. This hormone has been found to possess neuroprotective properties which is in association with its antioxidant and mitochondrial protection activity. Studying and exploring the signaling pathways which mediate pleotropic responses intracellularly have elucidated significant therapeutic approach in treatment and management of neurological disorders by IGF-I. The current review highlights the role of IGF-I in management of major neurological disorders such as depression, Parkinson's disease, and Alzheimer's disease and also covers the mechanisms involved in the process., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alcoholic neuropathy emerges following the persistent alcohol imbibing, and triggers nerve damage through de-escalating the receptors situated in the central nervous system (CNS), which consecutively evolves into debilitating neuropathic state and further precipitates hyperalgesia, allodynia, dysesthesia, ataxia, numbness, immobility, and decline in certain body functions. Existing pharmacotherapy, such as anticonvulsants (gabapentin and topiramate), and antidepressant drugs (duloxetine, and venlafaxine) render short-lasting benefits; however, their continual use is not favoured nowadays because of their detrimental outcomes and habit-forming behaviour. Consequently, the research is being shifted towards exploring novel propitious targets which entirely assist in the cessation of the disease. This review discloses the multitudinous pathways implicated in the pathogenesis of alcoholic neuropathy, with special emphasis on purinergic and orexinergic receptors. Moreover, the review focuses on targeting purinergic (P2X 3 , P2X 2/3 , P2X 4 , P2X 7 , and P2Y 12 ), and orexinergic (OX1 and OX2) receptors associated with the evolution of alcoholic neuropathy, and to incentivize further investigation to attain novel propitious strategy in alcoholic neuropathy treatment. The mechanisms implicated in the progression of alcoholic neuropathy comprises malnourishment (B vitamins scarcity), direct pernicious outcomes of alcohol, increased oxidative-nitrosative stress, protein kinase C epsilon (PKCε), and extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) functioning, abnormalities in the axonal transport and cytoskeleton system, activation of nuclear factor-kappa B (NF-κB) and caspase pathway, stimulation of the sympathoadrenal and hypothalamo-pituitary-adrenal (HPA) axis, and microglial cells of spinal column. The purinergic receptor antagonists, orexins/orexinergic receptor antagonists eliminate/modulate hyperalgesia, allodynia, inflammatory pain, liberation of inflammatory mediators, NF-κB signalling pathway, ROS formation, nerve cell deterioration, and craving for alcohol consumption, thereby ceasing the evolution of alcoholic neuropathy. The authors focus to highlight the importance of this alternative strategy as a novel target in alcoholic neuropathy, and to incentivize researchers to scrutinize the possible benefits of purinergic and orexins/orexinergic receptors in the therapy of alcoholic neuropathy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Parkinson's disease (PD) is a neurodegenerative disease affecting about 2% of the population. A neuropeptide, orexin, is linked with sleep abnormalities in the parkinsonian patient. This study aimed to review the changes in the orexinergic system in parkinsonian subjects and the effects of orexin. A number of search techniques were used and presumed during the search, including cloud databank searches of PubMed and Medline using title words, keywords, and MeSH terms. PD is characterised by motor dysfunctions (postural instability, rigidity, tremor) and cognitive disorders, sleep-wake abnormalities grouped under non-motor disorders. The Orexinergic system found in the hypothalamus is linked with autonomic function, neuroprotection, learning and memory, and the sleep-wake cycle. Prepro-orexin, a precursor peptide (130 amino acids), gives rise to orexins (Orx-A and Orx-B). Serum orexin level measurement is vital for evaluating several neurological disorders (Alzheimer's disease, Huntington's disease, and PD). Orexinergic neurons are activated by hypoglycemia and ghrelin, while they are restrained by food consumption and leptin. Orexinergic system dysfunctioning was found to be linked with non-motor symptoms (sleep abnormalities) in PD. Orexinergic neuron's behaviour may be either inhibitory or excitatory depending on the environment in which they are present. As well, orexin antagonists are found to improve the abnormal sleep pattern. Since the orexinergic system plays a role in several psychological and neurological disorders, therefore, these disorders can be managed by targeting this system., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alzheimer's disease (AD) is a chronic and devastating neurodegenerative disorder that is affecting elderly people at an increasing rate. Clusterin (CLU), an extracellular chaperone, is an ubiquitously expressed protein that can be identified in various body fluids and tissues. Expression of CLU can lead to various processes including suppression of complement system, lipid transport, chaperone function, and also controlling neuronal cell death and cell survival mechanisms. Studies have confirmed that the level of CLU expression is increased in AD. Furthermore, CLU also decreased the toxicity and aggregation of amyloid beta (Aβ). However when the Aβ level was far greater than CLU, then the amyloid generation was increased. CLU was also found to incorporate in the amyloid aggregates, which were more harmful as compared with the Aβ42 aggregates alone. Growing evidence indicates that CLU plays roles in AD pathogenesis via various processes, including aggregation and clearance of Aβ, neuroinflammation, lipid metabolism, Wnt signaling, copper homeostasis, and regulation of neuronal cell cycle and apoptosis. In this article, we represent the critical interaction of CLU and AD based on recent advances. Furthermore, we have also focused on the Aβ-dependent and Aβ-independent mechanisms by which CLU plays a role in AD pathogenesis., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)