The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneratio...The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor （NGF） al- terations in sporadic Alzheimer＇s disease （AD）, an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons （BFCN）, is one of the first homeostatic systems affected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neuro- trophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario： NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. The recent acceleration in the characterization of anatomical, functional and molecular profiles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the sep- to-hippocampal system is crucial for the identification of new target molecules to slow and eventually halt mild cognitive impairment （MCI） and its progression toward AD.展开更多
Tau is the prime participant in the Alzheimer’s disease(AD) neurodegeneration:AD,the main cause of dementia in elderly people,is a multifactorial neurodegenerative disorder characterized by a long prodromal phase(sta...Tau is the prime participant in the Alzheimer’s disease(AD) neurodegeneration:AD,the main cause of dementia in elderly people,is a multifactorial neurodegenerative disorder characterized by a long prodromal phase(starting more than two decades before clinical symptoms appear)with brain accumulation/misfolding of amyloidβ(Aβ)in insoluble amyloid plaques and of tau protein in neurofibrillary tangles.展开更多
基金supported by Ministry of Education,Universities and Research(MIUR/FIRB)funding to PC
文摘The current idea behind brain pathology is that disease is initiated by mild disturbances of common physiological processes. Overtime, the disruption of the neuronal homeostasis will determine irreversible degeneration and neuronal apoptosis. This could be also true in the case of nerve growth factor （NGF） al- terations in sporadic Alzheimer＇s disease （AD）, an age-related pathology characterized by cholinergic loss, amyloid plaques and neurofibrillary tangles. In fact, the pathway activated by NGF, a key neurotrophin for the metabolism of basal forebrain cholinergic neurons （BFCN）, is one of the first homeostatic systems affected in prodromal AD. NGF signaling dysfunctions have been thought for decades to occur in AD late stages, as a mere consequence of amyloid-driven disruption of the retrograde axonal transport of neuro- trophins to BFCN. Nowadays, a wealth of knowledge is potentially opening a new scenario： NGF signaling impairment occurs at the onset of AD and correlates better than amyloid load with cognitive decline. The recent acceleration in the characterization of anatomical, functional and molecular profiles of early AD is aimed at maximizing the efficacy of existing treatments and setting novel therapies. Accordingly, the elucidation of the molecular events underlying APP metabolism regulation by the NGF pathway in the sep- to-hippocampal system is crucial for the identification of new target molecules to slow and eventually halt mild cognitive impairment （MCI） and its progression toward AD.
基金The present work was supported by in part by Fondo Ordinario Enti(FOE D.M865/2019)in the framework of a collaboration agreement between the Italian National Research Council and EBRI(2019-2021)(to PC)VL was supported by Post-doctoral Fellowship by Operatori Sanitari Assistiti(OSA).
文摘Tau is the prime participant in the Alzheimer’s disease(AD) neurodegeneration:AD,the main cause of dementia in elderly people,is a multifactorial neurodegenerative disorder characterized by a long prodromal phase(starting more than two decades before clinical symptoms appear)with brain accumulation/misfolding of amyloidβ(Aβ)in insoluble amyloid plaques and of tau protein in neurofibrillary tangles.
