Amyotrophic Lateral Sclerosis(ALS)is a complex neurodegenerative disorder characterized by progressive axonopathy,jointly leading to the dying back of the motor neuron,disrupting both nerve signaling and motor control...Amyotrophic Lateral Sclerosis(ALS)is a complex neurodegenerative disorder characterized by progressive axonopathy,jointly leading to the dying back of the motor neuron,disrupting both nerve signaling and motor control.In this review,we highlight the roles of axonopathy in ALS progression,driven by the interplay of multiple factors including defective trafficking machinery,protein aggregation,and mitochondrial dysfunction.Dysfunctional intracellular transport,caused by disruptions in microtubules,molecular motors,and adaptors,has been identified as a key contributor to disease progression.Aberrant protein aggregation involving TDP-43,FUS,SOD1,and dipeptide repeat proteins further amplifies neuronal toxicity.Mitochondrial defects lead to ATP depletion,oxidative stress,and Ca2+imbalance,which are regarded as key factors underlying the loss of neuromuscular junctions and axonopathy.Mitigating these defects through interventions including neurotrophic treatments offers therapeutic potential.Collaborative research efforts aim to unravel ALS complexities,opening avenues for holistic interventions that target diverse pathological mechanisms.展开更多
Mitochondrial disorders are phenotypically varied, with serious clinical repercussions. Among them, there is the deficiency of combined oxidative phosphorylation of type 20, which occurs due to a defect in the VARS2 g...Mitochondrial disorders are phenotypically varied, with serious clinical repercussions. Among them, there is the deficiency of combined oxidative phosphorylation of type 20, which occurs due to a defect in the VARS2 gene. This article presents a case of a 2-year-old female with progressive myoclonic epilepsy and psychomotor regression, with refractoriness to multiple anticonvulsants. The diagnosis was only made after the examination was carried out. Therefore, this article highlights the aspects of this rare disease and the importance of the exome for the diagnosis of rare conditions.展开更多
Axonal transport of mitochondria is critical for neuronal survival and function. Automatically quantifying and analyzing mitochondrial movement in a large quantity remain challenging. Here, we report an efficient meth...Axonal transport of mitochondria is critical for neuronal survival and function. Automatically quantifying and analyzing mitochondrial movement in a large quantity remain challenging. Here, we report an efficient method for imaging and quantifying axonal mitochondrial trans- port using microfluidic-chamber-cultured neurons together with a newly developed analysis package named ＂MitoQuant＂. This tool-kit consists of an automated program for tracking mitochondrial movement inside live neuronal axons and a transient-velocity analysis program for analyzing dynamic movement patterns of mitochondria. Using this method, we examined axonal mitochondrial movement both in cultured mammalian neurons and in motor neuron axons of Drosophila in vivo. In 3 different paradigms （temperature changes, drug treatment and genetic manipulation） that affect mitochondria, we have shown that this new method is highly efficient and sensitive for detecting changes in mitochondrial movement. The method significantly enhanced our ability to quantitatively analyze axonal mitochondrial movement and allowed us to detect dynamic changes in axonal mltochondrial transport that were not detected by traditional kymographic analyses.展开更多
基金supported by the National Natural Science Foundation of China(32271001 and 31871036).
文摘Amyotrophic Lateral Sclerosis(ALS)is a complex neurodegenerative disorder characterized by progressive axonopathy,jointly leading to the dying back of the motor neuron,disrupting both nerve signaling and motor control.In this review,we highlight the roles of axonopathy in ALS progression,driven by the interplay of multiple factors including defective trafficking machinery,protein aggregation,and mitochondrial dysfunction.Dysfunctional intracellular transport,caused by disruptions in microtubules,molecular motors,and adaptors,has been identified as a key contributor to disease progression.Aberrant protein aggregation involving TDP-43,FUS,SOD1,and dipeptide repeat proteins further amplifies neuronal toxicity.Mitochondrial defects lead to ATP depletion,oxidative stress,and Ca2+imbalance,which are regarded as key factors underlying the loss of neuromuscular junctions and axonopathy.Mitigating these defects through interventions including neurotrophic treatments offers therapeutic potential.Collaborative research efforts aim to unravel ALS complexities,opening avenues for holistic interventions that target diverse pathological mechanisms.
文摘Mitochondrial disorders are phenotypically varied, with serious clinical repercussions. Among them, there is the deficiency of combined oxidative phosphorylation of type 20, which occurs due to a defect in the VARS2 gene. This article presents a case of a 2-year-old female with progressive myoclonic epilepsy and psychomotor regression, with refractoriness to multiple anticonvulsants. The diagnosis was only made after the examination was carried out. Therefore, this article highlights the aspects of this rare disease and the importance of the exome for the diagnosis of rare conditions.
文摘Axonal transport of mitochondria is critical for neuronal survival and function. Automatically quantifying and analyzing mitochondrial movement in a large quantity remain challenging. Here, we report an efficient method for imaging and quantifying axonal mitochondrial trans- port using microfluidic-chamber-cultured neurons together with a newly developed analysis package named ＂MitoQuant＂. This tool-kit consists of an automated program for tracking mitochondrial movement inside live neuronal axons and a transient-velocity analysis program for analyzing dynamic movement patterns of mitochondria. Using this method, we examined axonal mitochondrial movement both in cultured mammalian neurons and in motor neuron axons of Drosophila in vivo. In 3 different paradigms （temperature changes, drug treatment and genetic manipulation） that affect mitochondria, we have shown that this new method is highly efficient and sensitive for detecting changes in mitochondrial movement. The method significantly enhanced our ability to quantitatively analyze axonal mitochondrial movement and allowed us to detect dynamic changes in axonal mltochondrial transport that were not detected by traditional kymographic analyses.
