Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by progressive death of motor neurons in the cortex, brainstem, and spinal cord. Until now, many treatment strategies have been tested in ALS, but so far only Riluzole has shown efficacy of slightly slowing disease progression. The pathophysiological mechanisms underlying ALS are multifactorial, with a complex interaction between genetic factors and molecular pathways. Other motor neuron disease such as spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA) are also progressive neurodegenerative disease with loss of motor neuron as ALS. This common thread of motor neuron loss has provided a target for the development of therapies for these motor neuron diseases. A better understanding of these pathogenic mechanisms and the potential pathological relationship between the various cellular processes have suggested novel therapeutic approaches, including stem cell and genetics-based strategies, providing hope for feasible treatment of ALS.
Amyotrophic Lateral Sclerosis* ; Brain Stem ; Disease Progression ; Hope ; Motor Neuron Disease ; Motor Neurons ; Muscular Atrophy, Spinal ; Muscular Disorders, Atrophic ; Neurodegenerative Diseases ; Riluzole ; Spinal Cord ; Stem Cells

In recent years, iron has been regarded as a common pathological feature of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Friedreich's ataxia (FRDA). A number of genes involved in iron transport, storage and regulation have been found associated with initiation and progression of neurodegeneration. However, whether iron abnormalities represent a primary or secondary event still remains unknown. Due to the limitation in transgenic rodent model construction and transfection systems, the progress in unraveling the pathogenic role of different iron-related proteins in neurodegenerative diseases has been slow. Drosophila melanogaster, a simple organism which has a shorter lifespan and smaller genome with many conserved genes, and captures many features of human nervous system and neurodegeneration, may help speed up the progress. The characteristics that spatial- and temporal-specific transgenic Drosophila can be easily constructed and raised in large quantity with phenotype easily determined turn Drosophila into an excellent in vivo genetic system for screening iron-related modifiers in different neurodegenerative conditions and hence provide a better picture about the pathogenic contribution of different iron-related protein abnormalities. It is believed that identification of important iron-related genes that can largely stop or even reverse degenerative process in Drosophila models may lead to development of novel therapeutic strategies against neurodegenerative diseases.
Alzheimer Disease ; physiopathology ; Animals ; Disease Models, Animal ; Drosophila melanogaster ; Friedreich Ataxia ; physiopathology ; Humans ; Iron ; Neurodegenerative Diseases ; physiopathology ; Parkinson Disease ; physiopathology

Neurodegenerative diseases are associated with neuroinflammation,oxidative stress,and aging,which can lead to cognitive and motor dysfunctions.Recent studies suggest that the development of neurodegenerative diseases is related to adaptive immunity,in which CD4
Alzheimer Disease ; Amyotrophic Lateral Sclerosis ; Humans ; Neurodegenerative Diseases ; Parkinson Disease ; T-Lymphocytes

Neurodegenerative diseases are the hereditary and sporadic conditions which are characterized by progressive neuronal degeneration. Neurodegenerative diseases are emerging as the leading cause of death, disabilities, and a socioeconomic burden due to an increase in life expectancy. There are many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis, but we have no effective treatments or cures to halt the progression of any of these diseases. Stem cell-based therapy has become the alternative option to treat neurodegenerative diseases. There are several types of stem cells utilized; embryonic stem cells, induced pluripotent stem cells, and adult stem cell (mesenchymal stem cells and neural progenitor cells). In this review, we summarize recent advances in the treatments and the limitations of various stem cell technologies. Especially, we focus on clinical trials of stem cell therapies for major neurodegenerative diseases.
Adult Stem Cells ; Alzheimer Disease ; Amyotrophic Lateral Sclerosis ; Cause of Death ; Cell Transplantation ; Embryonic Stem Cells ; Huntington Disease ; Induced Pluripotent Stem Cells ; Life Expectancy ; Multiple Sclerosis ; Neurodegenerative Diseases* ; Neurons ; Parkinson Disease ; Stem Cells*

No abstract available.
Amyotrophic Lateral Sclerosis* ; Charcot-Marie-Tooth Disease* ; China* ; Pedigree*

Recent studies suggest that alterations of the immune-inflammatory system contribute to the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Neuroinflammatory response initiated by innate immune mechanism that self-attack on neurons, known as "autotoxicity" could be an initial key mechanism of chronic neurodegenerative diseases. Numerous experimental and pathological evidences showing upregulated inflammatory cytokines and chemokines, and the activation of complement cascade and accumulation of activated microglia in damaged regions support the important role of immune-inflammatory mechanism in the pathogenesis of neurodegenerative diseases. Epidemiological studies on the non-steroidal anti-inflammatory drugs (NSAIDs), coupled with results from animal model of AD, PD and ALS, have prompted the studies to determine if immune-inflammatory modifying agents or molecules could be a new therapeutic paradigm of neurodegenerative diseases. Molecules inhibiting proinflammatory cytokines and chemokines released from microglia, agents that inhibit activation of microglia, COX2 and complement system are now considered as a good candidate of immune-inflammatory modulating treatment. By better understanding inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approach that may not completely cure AD, PD, and ALS but will likely help slow the progression or delay the onset of these devastating diseases.
Alzheimer Disease* ; Amyotrophic Lateral Sclerosis ; Chemokines ; Complement System Proteins ; Cytokines ; Microglia ; Models, Animal ; Neurodegenerative Diseases ; Neurons ; Parkinson Disease

BACKGROUND: Over activation of the DNA repairing enzyme, poly (ADP-ribose) polymerase (PARP) in response to oxidative damage of DNA appears to play a role in cellular death in neurodegenerative diseases. Previous data suggested that PARP immunoreactivity (IR) was increased in the white and gray matter in spinal cord of the sporadic amyotrophic lateral sclerosis (sALS), predominantly in cells with astroglial morphology. METHODS: In the present study, we evaluated whether the PARP expression was present widespread in various regions of brain tissue including the motor cortex, parietal cortex and cerebellum. RESULTS: By western blot, PARP-IR in motor cortex from sALS patients, compared to the same region from age-matched normal controls, was also significantly increased (p=0.006). Importantly, PARP-IR was also increased in the parietal cortex, and cerebellum of sALS patients compared to the controls, in regions that are usually clinically unaffected in ALS (p=0.043, p=0.035, respectively). In addition, increased PARP expression in ALS was more prominent compared to Alzheimer's brain. Immunohistochemistry revealed that PARP staining was more significant in the cortical neurons and in the subcortical white matter glial cells from sALS patients compared to normal controls and Alzheimer's disease. CONCLUSIONS: The data demonstrate that increase in PARP-IR is not limited only to the vulnerable motor cortex. Furthermore, PARP-IR is present in both cortical neuronal and subcortical glial cells. The data suggest that widespread cellular stress on neuronal and glial cells is present in the brain of sporadic ALS patients.
Alzheimer Disease ; Amyotrophic Lateral Sclerosis* ; Blotting, Western ; Brain* ; Cerebellum ; DNA ; DNA Repair ; Humans ; Immunohistochemistry ; Motor Cortex ; Motor Neurons ; Neurodegenerative Diseases ; Neuroglia ; Neurons* ; Rabeprazole ; Spinal Cord

Iron is an important element for brain oxygen transport, myelination, DNA synthesis and neurotransmission. However, excessive iron can generate reactive oxygen species and contribute neurotoxicity. Although brain iron deposition is the natural process with normal aging, excessive iron accumulation is also observed in various neurological disorders such as neurodegeneration with brain iron accumulation, Parkinson's disease, Alzheimer's disease, multiple sclerosis, Friedreich ataxia, and others. Magnetic resonance image (MRI) is a useful method for detecting iron deposits in the brain. It can be a powerful tool for diagnosis and monitoring, while furthering our understanding of the role of iron in the pathophysiology of a disease. In this review, we will introduce the mechanism of iron toxicity and the basics of several iron-related MRI techniques. Also, we will summarize the previous results concerning the clinical application of such MR imagings in various neurological disorders.
Aging ; Alzheimer Disease ; Brain ; Diagnosis ; DNA ; Friedreich Ataxia ; Iron* ; Magnetic Resonance Imaging* ; Multiple Sclerosis ; Myelin Sheath ; Nervous System Diseases* ; Neurodegenerative Diseases ; Oxygen ; Parkinson Disease ; Reactive Oxygen Species ; Synaptic Transmission

OBJECTIVE: To analyze the distribution characteristics of hereditary peripheral neuropathy (HPN) pathogenic genes in Chinese Han population, and to explore the potential pathogenesis and treatment prospects of HPN and related diseases. METHODS: Six hundred and fifty-six index patients with HPN were enrolled in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to May 2022. The PMP22 duplication and deletion mutations were screened and validated by multiplex ligation probe amplification technique. The next-generation sequencing gene panel or whole exome sequencing was used, and the suspected genes were validated by Sanger sequencing. RESULTS: Charcot-Marie-Tooth (CMT) accounted for 74.3% (495/666) of the patients with HPN, of whom 69.1% (342/495) were genetically confirmed. The most common genes of CMT were PMP22 duplication, MFN2 and GJB1 mutations, which accounted for 71.3% (244/342) of the patients with genetically confirmed CMT. Hereditary motor neuropathy (HMN) accounted for 16.1% (107/666) of HPN, and 43% (46/107) of HPN was genetically confirmed. The most common genes of HMN were HSPB1, aminoacyl tRNA synthetases and SORD mutations, which accounted for 56.5% (26/46) of the patients with genetically confirmed HMN. Most genes associated with HMN could cause different phenotypes. HMN and CMT shared many genes (e.g. HSPB1, GARS, IGHMBP2). Some genes associated with dHMN-plus shared genes associated with amyotrophic lateral sclerosis (KIF5A, FIG4, DCTN1, SETX, VRK1), hereditary spastic paraplegia (KIF5A, ZFYVE26, BSCL2) and spinal muscular atrophy (MORC2, IGHMBP, DNAJB2), suggesting that HMN was a continuum rather than a distinct entity. Hereditary sensor and autosomal neuropathy (HSAN) accounted for a small proportion of 2.6% (17/666) in HPN. The most common pathogenic gene was SPTLC1 mutation. TTR was the main gene causing hereditary amyloid peripheral neuropathy. The most common types of gene mutations were p.A117S and p.V50M. The symptoms were characterized by late-onset and prominent autonomic nerve involvement. CONCLUSION CMT and HMN are the most common diseases of HPN. There is a large overlap between HMN and motor-CMT2 pathogenic genes, and some HMN pathogenic genes overlap with amyotrophic lateral sclerosis, hereditary spastic hemiplegia and spinal muscular atrophy, suggesting that there may be a potential common pathogenic pathway between different diseases.
Amyotrophic Lateral Sclerosis ; Charcot-Marie-Tooth Disease/genetics* ; DNA Helicases/genetics* ; DNA-Binding Proteins/genetics* ; Flavoproteins ; HSP40 Heat-Shock Proteins ; Humans ; Intracellular Signaling Peptides and Proteins/genetics* ; Kinesins ; Ligases/genetics* ; Molecular Chaperones ; Multifunctional Enzymes ; Muscular Atrophy, Spinal/genetics* ; Mutation ; Phosphoric Monoester Hydrolases ; Protein Serine-Threonine Kinases ; RNA Helicases/genetics* ; RNA, Transfer ; Transcription Factors/genetics*

Neurodegenerative diseases such as Parkinson's disease and amyotrophic lateral sclerosis may induce impairment of speech motor system. This review discusses the characteristics of dysarthria and symptom management for these conditions. Given the progressive nature of the neurodegenerative diseases, speech–language pathologists must be aware of appropriate augmentative and alternative communication equipment at the early stage of the disease course. Patients with neurodegenerative diseases can maintain functional communication with augmentative and alternative communication supports.
Amyotrophic Lateral Sclerosis ; Dysarthria ; Humans ; Neurodegenerative Diseases* ; Parkinson Disease ; Rehabilitation*