Parkinson disease (PD) is a neurodegenerative disease characterized by the selective loss of dopaminergic neurons from the substantia nigra pars compacta leading to the impairment of motor functions. Recent genetic studies have uncovered several genes involved in inherited forms of the disease. These gene products are likely to be implicated in the biochemical pathways underlying the etiology of sporadic PD. Our review discusses the pathogenetic mechanisms of the mutated genes.
Dopaminergic Neurons ; Genetics ; Neurodegenerative Diseases ; Parkinson Disease* ; Substantia Nigra

As the most common neurodegenerative disease, Alzheimer's disease (AD) is characterized by progressive cognitive decline and is a major threat to the health of elderly worldwide. Aside from its pathogenesis, delineation of the protective mechanism of AD is also critical for the etiological treatment. AD resilience refers to a protective mechanism which can maintain the cognitive intactness of patients despite of genetic risk factors and/or related pathology. Studies on the genetic mechanism of AD resilience are of great importance for revealing novel mechanisms and therapeutic targets, as well as optimizing polygenic risk score which can facilitate early identification and intervention for individuals at risk.
Aged ; Humans ; Alzheimer Disease/genetics* ; Neurodegenerative Diseases ; Cognitive Dysfunction

Amyotrophic lateral sclerosis (ALS) is a relentless, progressive, and presently incurable neurodegenerative disease. Its drug development has been hampered by the lack of effective biomarkers for early diagnosis, progression and prognosis. Recently, significant progress has been made for the identification of body fluid biomarkers for ALS, which conferred both theoretical and practical feasibility for the early diagnosis and progression monitoring. Meanwhile, it also facilitated identification of genes and/or pathways for the pathogenesis of ALS. This review summarized biomarkers identified from cerebrospinal fluid, blood and urine of ALS patients and their clinical implications.
Amyotrophic Lateral Sclerosis/genetics* ; Biomarkers ; Humans ; Neurodegenerative Diseases ; Prognosis

Polyglutamine(PolyQ) diseases comprise a group of inherited neurodegenerative disorders with significant clinical and genetic heterogeneity. Although they share a common mechanism involving dynamic expansion of CAG trinucleotide repeats, their clinical features may vary and there has been no specific treatment. Recently, much attention had been attracted to microRNAs which, as a new type of posttranscription regulatory factor, have proven to significantly affect the progress of PolyQ disease. This review will focus on the roles of microRNAs in the pathogenesis of PolyQ diseases and their potential use for therapy.
Humans ; MicroRNAs ; genetics ; Neurodegenerative Diseases ; genetics ; Peptides ; genetics ; Trinucleotide Repeats ; genetics

Alzheimer's disease (AD) is the most common senile neurodegenerative disease characterized by progressive cognitive dysfunction, psychological and behavioral abnormalities, and impaired ability of activities of daily living. A family with a total of 3 patients were admitted to the Department of Neurology of Xiangya Hospital, Central South University in 2018. The proband showed memory decline as the presenting symptoms, and subsequently showed psychological and behavioral abnormalities, personality changes, seizures, and motor retardation. Definite diagnosis of early-onset familial AD (EOFAD) with missense mutation of presenilin 2 (PSEN2) (c.715A>G p.M239V) was established by whole exome sequencing (WES) technology. We reported the mutation in Chinese Han population for the first time, which expanded the mutation spectrum ofPSEN2 gene and aid to enrich the characterization of clinical phenotype in EOFAD associated to PSEN2 mutations. Patients with early onset age and complex clinical manifestations of AD can be diagnosed with the help of genetic testing to avoid misdiagnosis.
Activities of Daily Living ; Alzheimer Disease/genetics* ; Humans ; Mutation ; Neurodegenerative Diseases ; Presenilin-1/genetics* ; Presenilin-2/genetics*

Neurodegenerative diseases are a group of chronic progressive neuronal damage disorders. The cause is unclear, most of them share a same pathological hallmark with misfold proteins accumulating in neurons. Carboxyl-terminus of Hsc70 interacting protein (CHIP) is a dual functional molecule, which has a N terminal tetratrico peptide repeat (TPR) domain that interacts with Hsc/Hsp70 complex and Hsp90 enabling CHIP to modulate the aberrant protein folding; and a C terminal U-box ubiquitin ligase domain that binds to the 26S subunit of the proteasome involved in protein degradation via ubiqutin-proteasome system. CHIP protein mediates interactions between the chaperone system and the ubiquitin-proteasome system, and plays an important role in maintaining the protein homeostasis in cells. This article reviews the molecular characteristics and physiological functions of CHIP, and its role in cellular metabolism and discusses the relationship between CHIP dysfunction and neurodegenerative diseases.
Animals ; Humans ; Neurodegenerative Diseases ; genetics ; metabolism ; Protein Binding ; Protein Folding ; Proteolysis ; Ubiquitin-Protein Ligases ; genetics ; metabolism

Transglutaminase (TG) is a kind of calcium-dependent enzymes. The TGase family found in rodents and human contains 9 types, including TG1-7, blood coagulation factor XIIIa and erythrocyte membrane protein 4.2, with the former 8 types possessing catalytic activity. TG catalyzes various conversion reactions of glutamine, including transamination, deamination and esterification, and participates in post-transcriptional modification of proteins such as cross-linking peptides glutamine residue and lysyl-residue, stabilizing protein structure and catalyzing formation of protein aggregates. TGase has been found to contribute to a variety of important physiological and pathological processes and play a role in the pathogenesis of multiple diseases. Notably, neurodegenerative diseases such as Huntington's disease, spinocerebellar ataxia, Alzheimer's disease and Parkinson's disease, have a close connection with TGase's role in the human body.
Animals ; Brain ; enzymology ; Humans ; Neurodegenerative Diseases ; enzymology ; genetics ; Transglutaminases ; genetics ; metabolism

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which is associated with genetic and environmental factors, though the pathogenesis is still unclear and there is also a lack of effective treatment. With the rapid advance of genetic testing techniques, over 30 genes have been associated with the disease. Some ALS patients harboring genetic variants may present unique clinical characteristics and particular mode of inheritance, but the correlation between genotype and phenotype is still not very clear. Studies have shown that research on the pathogenic genes of ALS is important for the diagnosis and selection of potential drug targets. Here the pathogenic genes of ALS, in particular the newly discovered genes, and their underlying mechanisms are reviewed. The necessity of genetic testing for ALS patients is also stressed.
Amyotrophic Lateral Sclerosis/genetics* ; Genetic Testing ; Genotype ; Humans ; Neurodegenerative Diseases/genetics* ; Phenotype

In neuronal system, epigenetic modifications are essential for neuronal development, the fate determination of neural stem cells and neuronal function. The dysfunction of epigenetic regulation is closely related to occurrence and development of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease. Abnormally elevated DNA methylation inhibits the expression of some DNA repair-related genes and affects the progression of Huntington's disease. In the brain of Alzheimer's disease patients, the levels of H3K27ac and H3K9ac histone modifications increased. In addition, the alteration of RNA methylation in animal models of Alzheimer's disease and Parkinson's disease showed discrepancy trends. Therefore, epigenetic modifications may serve as potential therapeutic targets for neurodegenerative diseases. Here, we summarize the recent progress of the roles of epigenetic modifications in neurodegenerative diseases.
Animals ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Neurodegenerative Diseases/genetics* ; Parkinson Disease/genetics* ; Protein Processing, Post-Translational

Alzheimer's disease(AD) is a chronic progressive neurodegenerative disease with recent memory impairment as the main clinical manifestation and senile plaques and neurofibrillary tangles as the main pathological changes. In recent years, the effect of microRNAs on AD has attracted widespread attention. Patients with AD have abnormal expression of miRNA, which is closed related to regulation of AD pathophysiology-related genes. Therefore, this paper first elaborated neuroprotective and toxic effects of microRNA in AD, and then explored relevant traditional Chinese medicines that can regulate miRNA in the treatment of AD, so as to provide basis for revealing the pathogenesis relationship between miRNA and AD and provide ideas for further development of anti-AD traditional Chinese medicine.
Alzheimer Disease/genetics* ; Humans ; Medicine, Chinese Traditional ; MicroRNAs/genetics* ; Neurodegenerative Diseases