Nicotinamide adenine dinucleotide（NADH） in its reduced form of is a key coenzyme in redox reactions, essential for maintaining energy homeostasis.NADH and its oxidized counterpart, NAD+, form a redox couple that regulates various biological processes, including calcium homeostasis, synaptic plasticity, anti-apoptosis, and gene expression. The reduction of NAD+/NADH levels is closely linked to mitochondrial dysfunction, which plays a pivotal role in the cascade of various neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease.Auditory neuropathy（AN） is recognized as a clinical biomarker in neurodegenerative disorders. Furthermore, mitochondrial dysfunction has been identified in patients with mutations in genes like OPA1and AIFM1. However, effective treatments for these conditions are still lacking. Increasing evidence suggests that administratering NAD+ or its precursors endogenously may potentially prevent and slow disease progression by enhancing DNA repair and improving mitochondrial function. Therefore, this review concentrates on the metabolic pathways of NAD+/NADH production and their biological functions, and delves into the therapeutic potential and mechanisms of NADH in treating AN.
Humans ; NAD/metabolism* ; Neurodegenerative Diseases/metabolism* ; Mitochondria ; Oxidation-Reduction ; Mitochondrial Diseases

Background: Creutzfeldt-Jakob disease is a rapidly progressive, fatal, transmissible neurodegenerative disorder caused by a prion protein. It is characterized by cognitive decline, motor dysfunction, and eventually, death. It occurs globally with 1 case per one million population/year. And It is still considered rare in countries like the Philippines due to challenges in its diagnosis and the under recognition of its clinical features. As of now, the local prevalence or incidence of this disease in our country remains unknown, as only a single case report has been documented. As of now, the local prevalence or incidence of this disease in our country remains unknown, as only a single case report has been documented. Objective: To report a series of patients with probable sporadic CJD from a tertiary hospital in the Philippines. Materials and Methods: Patients with rapidly developing dementia fulfilling the diagnostic criteria for sCJD were included. All were investigated in detail to find out any possible treatable cause, including electroencephalography (EEG), magnetic resonance imaging (MRI) of the brain, and cerebrospinal fluid analysis. Results: A total of 3 patients with probable sCJD were diagnosed using the European diagnostic criterion from January 2022 to April 2023. The clinical features are consistent with other reported series. All 3 patients had the classical EEG findings, typical MRI features, and positive for 14-3-3 assay, and one was positive for RT-QuIC. Two patients died within 13 months from the disease onset. Conclusion This is the first reported case series of probable sCJD in the Philippines from a tertiary hospital in Metro Manila. Like in our patients, this disease should be considered in individuals with rapidly progressive dementia associated with myoclonus, neuropsychiatric symptoms, akinetic mutism, visual abnormality, and ataxia with signs of pyramidal and extra-pyramidal dysfunction. Although a definitive diagnosis must be histopathological, there are ancillary tests that are currently available that allow us to make a probable diagnosis of sCJD possible. Our study raises question about the prevalence of this disease in the Philippines which needs more validated studies from other parts of the country.
Creutzfeldt-Jakob Syndrome ; Neurodegenerative Diseases

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
Humans ; Prions ; Neurodegenerative Diseases/pathology* ; Amyloid beta-Peptides ; Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; Parkinson Disease

Previous studies mainly used β-amyloid and α-synuclein as the biomarkers for the diagnosis of neurodegenerative diseases. In recent years，studies have shown that telomeres at the end of chromosome can be used as an index to measure the degree of biological aging，and telomere length and telomerase activity may also be used as the blood markers to evaluate the risk，progression，and poor prognosis of neurodegenerative diseases in the elderly；however，there is still a lack of consistency between the research findings in China and globally. Understanding the role of telomere-related biomarkers in age-related diseases can help clinicians learn more about the mechanism of disease development and progression. This article reviews the latest research advances in the telomere-telomerase system in neurodegenerative diseases，in order to introduce the influence of telomere length and telomerase activity on neurodegenerative diseases and their potential mechanisms of action.
Telomere ; Telomerase ; Neurodegenerative Diseases ; Alzheimer Disease ; Parkinson Disease

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset, posing a serious threat to human physical and mental health. The cognitive impairments caused by AD are generally diffuse and overlap symptomatically with other neurodegenerative diseases. Moreover, the symptoms of AD are often covert, leading to missed opportunities for optimal treatment after diagnosis. Therefore, early diagnosis of AD is crucial. In vitro diagnostic biomarkers not only contribute to the early clinical diagnosis of AD but also aid in further understanding the disease's pathogenesis, predicting disease progression, and observing the effects of novel candidate therapeutic drugs in clinical trials. Currently, although there are numerous biomarkers associated with AD diagnosis, the complex nature of AD pathogenesis, limitations of individual biomarkers, and constraints of clinical detection methods have hindered the development of efficient, cost-effective, and convenient diagnostic methods and standards. This article provides an overview of the research progress on in vitro diagnostic biomarkers and detection methods related to AD in recent years.
Humans ; Alzheimer Disease/diagnosis* ; Neurodegenerative Diseases ; Early Diagnosis ; Cognitive Dysfunction ; Biomarkers

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset, posing a serious threat to human physical and mental health. The cognitive impairments caused by AD are generally diffuse and overlap symptomatically with other neurodegenerative diseases. Moreover, the symptoms of AD are often covert, leading to missed opportunities for optimal treatment after diagnosis. Therefore, early diagnosis of AD is crucial. In vitro diagnostic biomarkers not only contribute to the early clinical diagnosis of AD but also aid in further understanding the disease's pathogenesis, predicting disease progression, and observing the effects of novel candidate therapeutic drugs in clinical trials. Currently, although there are numerous biomarkers associated with AD diagnosis, the complex nature of AD pathogenesis, limitations of individual biomarkers, and constraints of clinical detection methods have hindered the development of efficient, cost-effective, and convenient diagnostic methods and standards. This article provides an overview of the research progress on in vitro diagnostic biomarkers and detection methods related to AD in recent years.
Humans ; Alzheimer Disease/diagnosis* ; Neurodegenerative Diseases ; Early Diagnosis ; Cognitive Dysfunction ; Biomarkers

Understanding the fundamental processes of human brain development and diseases is of great importance for our health. However, existing research models such as non-human primate and mouse models remain limited due to their developmental discrepancies compared with humans. Over the past years, an emerging model, the "brain organoid" integrated from human pluripotent stem cells, has been developed to mimic developmental processes of the human brain and disease-associated phenotypes to some extent, making it possible to better understand the complex structures and functions of the human brain. In this review, we summarize recent advances in brain organoid technologies and their applications in brain development and diseases, including neurodevelopmental, neurodegenerative, psychiatric diseases, and brain tumors. Finally, we also discuss current limitations and the potential of brain organoids.
Animals ; Mice ; Humans ; Induced Pluripotent Stem Cells ; Brain/pathology* ; Disease Models, Animal ; Neurodegenerative Diseases/pathology* ; Organoids/pathology*

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg^-1) for five days, followed by BBP (50, 100, and 200 mg·kg^-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.
Humans ; Mice ; Rats ; Animals ; Aged ; Middle Aged ; Parkinson Disease/pathology* ; Astrocytes/pathology* ; Powders/therapeutic use* ; Ursidae/metabolism* ; NF-kappa B/metabolism* ; Neuroinflammatory Diseases ; Neurodegenerative Diseases/metabolism* ; Cyclooxygenase 2/metabolism* ; Lipopolysaccharides/pharmacology* ; Bile ; Mice, Inbred C57BL ; Microglia ; Disease Models, Animal

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor symptoms, including bradykinesia, resting tremor, and progressive rigidity. More recently, non-motor symptoms of PD, such as pain, depression and anxiety, and autonomic dysfunction, have attracted increasing attention from scientists and clinicians. As one of non-motor symptoms, pain has high prevalence and early onset feature. Because the mechanism of PD-related pathological pain is unclear, the clinical therapy for treating PD-related pathological pain is very limited, with a focus on relieving the symptoms. This paper reviewed the clinical features, pathogenesis, and therapeutic strategies of PD-related pathological pain and discussed the mechanism of the chronicity of PD-related pathological pain, hoping to provide useful data for the study of drugs and clinical intervention for PD-related pathological pain.
Humans ; Parkinson Disease/therapy* ; Neurodegenerative Diseases ; Autonomic Nervous System Diseases/complications* ; Anxiety ; Pain/etiology*

Guanine nucleotide exchange factor Kalirin-7 (Kal-7) is a key factor in synaptic plasticity and plays an important regulatory role in the brain. Abnormal synaptic function leads to the weakening of cognitive functions such as learning and memory, accompanied by abnormal expression of Kal-7, which in turn induces a variety of neurodegenerative diseases. Exercise can upregulate the expression of Kal-7 in related brain regions to alleviate neurodegenerative diseases. By reviewing the literature on Kal-7 and neurodegenerative diseases, as well as the research progress of exercise intervention, this paper summarizes the role and possible mechanism of Kal-7 in the improvement of neurodegenerative diseases by exercise and provides a new rationale for the basic and clinical research on the prevention and treatment of neurodegenerative diseases by exercise.
Humans ; Neurodegenerative Diseases/therapy* ; Guanine Nucleotide Exchange Factors/metabolism* ; Exercise Therapy