Between destiny and disease: genetics and molecular pathways of human central nervous system aging.


:Aging of the human brain is associated with "normal" functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human post-mortem brain microarray studies, which we hypothesize, point to a potential genetically controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches.


Prog Neurobiol


Progress in neurobiology


Glorioso C,Sibille E




Has Abstract


2011-02-01 00:00:00














  • Hippocampal network dysfunction as a mechanism of early-onset dementia after preeclampsia and eclampsia.

    abstract::Preeclampsia is a hypertensive disorder of pregnancy that can involve dangerous neurological symptoms such as spontaneous seizures (eclampsia). Despite being diseases specific to the pregnant state, preeclampsia and eclampsia have long-lasting neurological consequences later in life, including changes in brain structu...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章


    authors: Johnson AC,Li Z,Orfila JE,Herson PS,Cipolla MJ

    更新日期:2020-10-29 00:00:00

  • Multiple functions of neuronal plasma membrane neurotransmitter transporters.

    abstract::Removal from receptors of neurotransmitters just released into synapses is one of the major steps in neurotransmission. Transporters situated on the plasma membrane of nerve endings and glial cells perform the process of neurotransmitter (re)uptake. Because the density of transporters in the membranes can fluctuate, t...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Raiteri L,Raiteri M

    更新日期:2015-11-01 00:00:00

  • Why we sleep: the evolutionary pathway to the mammalian sleep.

    abstract::The cause of sleep is a complex question, which needs first, a clear distinction amongst the different meanings of a causal relationship in the study of a given behavior, second, the requisites to be met by a suggested cause, and third, a precise definition of sleep to distinguish behavioral from polygraphic sleep. Th...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Nicolau MC,Akaârir M,Gamundí A,González J,Rial RV

    更新日期:2000-11-01 00:00:00

  • Barrel cortex function.

    abstract::Neocortex, the neuronal structure at the base of the remarkable cognitive skills of mammals, is a layered sheet of neuronal tissue composed of juxtaposed and interconnected columns. A cortical column is considered the basic module of cortical processing present in all cortical areas. It is believed to contain a charac...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Feldmeyer D,Brecht M,Helmchen F,Petersen CC,Poulet JF,Staiger JF,Luhmann HJ,Schwarz C

    更新日期:2013-04-01 00:00:00

  • Mechanisms of physiological and epileptic HFO generation.

    abstract::High frequency oscillations (HFO) have a variety of characteristics: band-limited or broad-band, transient burst-like phenomenon or steady-state. HFOs may be encountered under physiological or under pathological conditions (pHFO). Here we review the underlying mechanisms of oscillations, at the level of cells and netw...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Jefferys JG,Menendez de la Prida L,Wendling F,Bragin A,Avoli M,Timofeev I,Lopes da Silva FH

    更新日期:2012-09-01 00:00:00

  • Brain iron metabolism: neurobiology and neurochemistry.

    abstract::New findings obtained during the past years, especially the discovery of mutations in the genes associated with brain iron metabolism, have provided key insights into the homeostatic mechanisms of brain iron metabolism and the pathological mechanisms responsible for neurodegenerative diseases. The accumulated evidence...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Ke Y,Qian ZM

    更新日期:2007-10-01 00:00:00

  • The functional organization of motor nerve terminals.

    abstract::Neuromuscular junctions (NMJs) have long been studied as particularly accessible examples of chemical synapses. Nonetheless, some important features of neuromuscular transmission are still poorly understood. One of these is the low statistical variability of the number of transmitter quanta released from motor nerve t...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Slater CR

    更新日期:2015-11-01 00:00:00

  • Beyond faithful conduction: short-term dynamics, neuromodulation, and long-term regulation of spike propagation in the axon.

    abstract::Most spiking neurons are divided into functional compartments: a dendritic input region, a soma, a site of action potential initiation, an axon trunk and its collaterals for propagation of action potentials, and distal arborizations and terminals carrying the output synapses. The axon trunk and lower order branches ar...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Bucher D,Goaillard JM

    更新日期:2011-09-01 00:00:00

  • Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: From history to the interaction with the monoaminergic systems.

    abstract::Parkinson's disease is the second most common neurodegenerative disorder, characterized by the manifestation of motor symptoms, which are mainly attributed to the degeneration of dopamine neurons in the pars compacta of substantia nigra. Based on advancements in the understanding of the pathophysiology of the disease,...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Faggiani E,Benazzouz A

    更新日期:2017-04-01 00:00:00

  • The midline glia of Drosophila: a molecular genetic model for the developmental functions of glia.

    abstract::The Midline Glia of Drosophila are required for nervous system morphogenesis and midline axon guidance during embryogenesis. In origin, gene expression and function, this lineage is analogous to the floorplate of the vertebrate neural tube. The expression or function of over 50 genes, summarised here, has been linked ...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Jacobs JR

    更新日期:2000-12-01 00:00:00

  • Neurotransmitter inactivation is important for the origin of nerve system in animal early evolution: a suggestion from genomic comparison.

    abstract::Metazoans possess complicated multicellular structure among the multicellularities of eukaryotes. One evolutionary pressure that permits such complexity relates to the directed and precise informational transmission performed by numerous synapses in neuron system. Neurotransmitter inactivations play essential roles in...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Wu Q,Gu X,Wang Y,Li N,Liu X,Wu C,Yu L,Gu X

    更新日期:2006-04-01 00:00:00

  • Somatosensory evoked potentials in man: differentiation of spinal pathways responsible for conduction from the forelimb vs hindlimb.

    abstract::This review suggests that a previously unrecognized spinal cord pathway may be of major importance in the conduction of the somatosensory evoked potential (SEP) from the lower limb in Man. The nerve fiber type activated by a "typical" peripheral nerve stimulus used in studying the SEP will activate the posterior tibia...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: York DH

    更新日期:1985-01-01 00:00:00

  • Mitochondrial dysfunction and oxidative stress in Parkinson's disease.

    abstract::Parkinson's disease (PD) is a movement disorder that is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta resulting in dopamine deficiency in the striatum. Although majority of the PD cases are sporadic several genetic mutations have also been linked to the disease...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Subramaniam SR,Chesselet MF

    更新日期:2013-07-01 00:00:00

  • Sex hormone activity in alcohol addiction: integrating organizational and activational effects.

    abstract::There are well-known sex differences in the epidemiology and etiopathology of alcohol dependence. Male gender is a crucial risk factor for the onset of alcohol addiction. A directly modifying role of testosterone in alcohol addiction-related behavior is well established. Sex hormones exert both permanent (organization...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章


    authors: Lenz B,Müller CP,Stoessel C,Sperling W,Biermann T,Hillemacher T,Bleich S,Kornhuber J

    更新日期:2012-01-01 00:00:00

  • From brainstem to cortex: computational models of saccade generation circuitry.

    abstract::The brain circuitry of saccadic eye movements, from brainstem to cortex, has been extensively studied during the last 30 years. The wealth of data gathered allowed the conception of numerous computational models. These models proposed descriptions of the putative mechanisms generating this data, and, in turn, made pre...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Girard B,Berthoz A

    更新日期:2005-11-01 00:00:00

  • John Eccles' pioneering role in understanding central synaptic transmission.

    abstract::This chapter deals with the central role that Sir John Eccles played in the elucidation of the mechanisms of synaptic transmission within the central nervous system during the three decades between the late 1930s and 1966. His seminal discoveries involved studies of synaptic input to spinal motoneurons using intracell...

    journal_title:Progress in neurobiology

    pub_type: 传,历史文章,杂志文章


    authors: Burke RE

    更新日期:2006-02-01 00:00:00

  • Pathophysiology of obsessive-compulsive disorder: a necessary link between phenomenology, neuropsychology, imagery and physiology.

    abstract::Obsessive-compulsive disorder (OCD) is characterized by repetitive intrusive thoughts and compulsive time-consuming behaviors classified into three to five distinct symptom dimensions including: (1) aggressive/somatic obsessions with checking compulsions; (2) contamination concerns with washing compulsions; (3) symmet...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Aouizerate B,Guehl D,Cuny E,Rougier A,Bioulac B,Tignol J,Burbaud P

    更新日期:2004-02-01 00:00:00

  • Radial glial cell heterogeneity--the source of diverse progeny in the CNS.

    abstract::Here, we discuss the identity, heterogeneity and functions of radial glial cells mostly in the developing central nervous system (CNS). First, we define radial glial cells by morphological, cell biological and molecular criteria as true glial cells, akin to astroglia. We then describe the appearance of radial glial ce...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Pinto L,Götz M

    更新日期:2007-09-01 00:00:00

  • The S-100: a protein family in search of a function.

    abstract::The S-100 is a group of low molecular weight (10-12 kD) calcium-binding proteins highly conserved among vertebrates. It is present in different tissues as dimers of homologous or different subunits (alpha, beta). In the nervous system, the S-100 exists as a mixture composed of beta beta and alpha beta dimers with the ...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Fanò G,Biocca S,Fulle S,Mariggiò MA,Belia S,Calissano P

    更新日期:1995-05-01 00:00:00

  • Small conductance calcium-activated potassium channels: from structure to function.

    abstract::The cloning of K(Ca)2 channels revealed three subtypes, with each displaying distinct but partially overlapping expression distributions in the mammalian CNS and periphery. Activation of K(Ca)2 channels leads to membrane hyperpolarization and inhibition of action potential firing. Block of K(Ca)2 channels has been sug...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Weatherall KL,Goodchild SJ,Jane DE,Marrion NV

    更新日期:2010-07-01 00:00:00

  • Progress in Parkinson's disease-where do we stand?

    abstract::Parkinson's disease was first described in 1817 by James Parkinson. It is one of the most common neurodegenerative disorders, affecting the nigrostriatal pathways involved in the control of movement. Since the introduction of L-DOPA as a therapy in the mid-1960s, clinical management of the symptoms has progressed, but...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Toulouse A,Sullivan AM

    更新日期:2008-08-01 00:00:00

  • Nano- and neurotoxicology: An emerging discipline.

    abstract::The present critical review analyzes the question of how nanoparticles from continuously growing industrial production and use of nanomaterials may impact human brain health. Available evidence suggests incomplete effectiveness of protective barriers of the brain against nanoparticles translocation to the brain. This ...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Bencsik A,Lestaevel P,Guseva Canu I

    更新日期:2018-01-01 00:00:00

  • The neurophysiology of sleep and waking: intracerebral connections, functioning and ascending influences of the medulla oblongata.

    abstract::This paper focuses on the successive historical papers related to medulla oblongata (M.O.) intracerebral connections, its activities and ascending influences regulating sleep waking behavior. The M.O. certainly influences the quantitative and qualitative processes of waking. However, its neurophysiological properties ...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Gottesmann C

    更新日期:1999-09-01 00:00:00

  • Proteomics in brain research: potentials and limitations.

    abstract::The advent of proteomics techniques has been enthusiastically accepted in most areas of biology and medicine. In neuroscience, a host of applications was proposed ranging from neurotoxicology, neurometabolism, determination of the proteome of the individual brain areas in health and disease, to name a few. Only recent...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Lubec G,Krapfenbauer K,Fountoulakis M

    更新日期:2003-02-01 00:00:00

  • Plasticity of cutaneous primary afferent projections to the spinal dorsal horn.

    abstract::Reorganization of the somatotopic map in the spinal dorsal horn may be elicited by a variety of deafferenting lesions, including transection of peripheral nerves or dorsal roots, or the application of neurotoxins. While such lesions give rise to a variety of neurochemical and morphological changes in the dorsal horn, ...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Wilson P,Kitchener PD

    更新日期:1996-02-01 00:00:00

  • Intrinsic primary afferent neurons of the intestine.

    abstract::After a long period of inconclusive observations, the intrinsic primary afferent neurons of the intestine have been identified. The intestine is thus equipped with two groups of afferent neurons, those with cell bodies in cranial and dorsal root ganglia, and these recently identified afferent neurons with cell bodies ...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Furness JB,Kunze WA,Bertrand PP,Clerc N,Bornstein JC

    更新日期:1998-01-01 00:00:00

  • Exercise as a therapeutic intervention for motor and non-motor symptoms in Parkinson's disease: Evidence from rodent models.

    abstract::Parkinson's disease (PD) is characterised by degeneration of dopaminergic neurons of the nigrostriatal pathway, which leads to the cardinal motor symptoms of the disease - tremor, rigidity and postural instability. A number of non-motor symptoms are also associated with PD, including cognitive impairment, mood disturb...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Crowley EK,Nolan YM,Sullivan AM

    更新日期:2019-01-01 00:00:00

  • The effects of psychotherapy on brain function: a systematic and critical review.

    abstract::Over the past two decades, the development of neuroimaging techniques has allowed the non-invasive investigation of neuroplastic changes associated with psychotherapeutic treatment. The aim of the present article is to present a systematic and critical review of longitudinal studies addressing the impact of psychother...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Barsaglini A,Sartori G,Benetti S,Pettersson-Yeo W,Mechelli A

    更新日期:2014-03-01 00:00:00

  • Structure and function of amyloid in Alzheimer's disease.

    abstract::This review is focused on the structure and function of Alzheimer's amyloid deposits. Amyloid formation is a process in which normal well-folded cellular proteins undergo a self-assembly process that leads to the formation of large and ordered protein structures. Amyloid deposition, oligomerization, and higher order p...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Morgan C,Colombres M,Nuñez MT,Inestrosa NC

    更新日期:2004-12-01 00:00:00

  • Exploring the mammalian neuromuscular system by analysis of mutations: spinal muscular atrophy and myotonia.

    abstract::Any biological structure can be studied using mutations that interfere either with its emergence or its function. We investigate spontaneous and induced mutations in the mouse that affect neuromuscular development and function. The wobbler mouse (phenotype WR, genotype wr/wr) suffers from muscular atrophy because of t...

    journal_title:Progress in neurobiology

    pub_type: 杂志文章,评审


    authors: Jockusch H,Kaupmann K,Gronemeier M,Schleef M,Klocke R

    更新日期:1994-02-01 00:00:00