ADNP
Activity-dependent neuroprotector homeobox protein (Activity-dependent neuroprotective protein) [ADNP1] [KIAA0784]
Publications[править]
Activity-dependent neuroprotective protein (ADNP) is essential for embryonic development with ADNP mutations leading to syndromic autism, coupled with intellectual disabilities and motor developmental delays. Here, mining human muscle gene-expression databases, we have investigated the association of ADNP transcripts with muscle aging. We discovered increased ADNP and its paralogue [[ADNP2]] expression in the vastus lateralis muscle of aged compared to young subjects, as well as altered expression of the ADNP and the [[ADNP2]] genes in bicep brachii muscle of elderly people, in a sex-dependent manner. Prolonged exercise resulted in decreased ADNP expression, and increased [[ADNP2]] expression in an age-dependent manner in the vastus lateralis muscle. ADNP expression level was further correlated with 49 genes showing age-dependent changes in muscle transcript expression. A high degree of correlation with ADNP was discovered for 24 genes with the leading gene/protein being NMNAT1 (nicotinamide nucleotide adenylyl transferase 1). Looking at correlations differentiating the young and the old muscles and comparing protein interactions revealed an association of ADNP with the cell division cycle 5-like protein (CDC5L), and an aging-muscle-related interactive pathway in the vastus lateralis. In the bicep brachii, very high correlation was detected with genes associated with immune functions as well as mitochondrial structure and function among others. Taken together, the results suggest a direct association of ADNP with muscle strength and implicate ADNP fortification in the protection against age-associated muscle wasting.
MeSH Terms
- Adult
- Aged, 80 and over
- Aging
- Female
- Homeodomain Proteins
- Humans
- Male
- Muscle, Skeletal
- Nerve Tissue Proteins
- Nicotinamide-Nucleotide Adenylyltransferase
- Physical Endurance
- Sarcopenia
- Transcription, Genetic
Keywords
- Aging
- Endurance exercise
- Sarcopenia
- Sex
- Transcription profile
ADNP is a protein necessary for brain development, important for brain plasticity, cognitive and social functioning, characteristics that are all impaired in autism and in the Adnp( /-) mouse model, in a sex-dependent manner. ADNP was originally discovered as a protein that is secreted from glial cells in response to vasoactive intestinal peptide (VIP). VIP is a major neuroprotective peptide in the CNS and PNS and was also associated with social recognition in rodents and aggression, pair-bonding and parental behaviors in birds. Comparative sequence alignment revealed high evolutionary conservation of ADNP in Chordata. Despite its importance in brain function, ADNP has never been studied in birds. Zebra finches (Taeniopygia guttata) are highly social songbirds that have a sexually dichotomous anatomical brain structure, with males demonstrating a developed song system, presenting a model to study behavior and potential sexually dependent fundamental differences. Here, using quantitative real time polymerase chain reaction (qRT-PCR), we discovered sexually dichotomous and age related differences in ADNP mRNA expression in three different regions of the song bird brain-cerebellum, cerebrum, and brain stem. Higher levels of ADNP mRNA were specifically found in young male compared to the female cerebrum, while aging caused a significant 2 and 3-fold decrease in the female and male cerebrum, respectively. Furthermore, a comparison between the three tested brain regions revealed unique sex-dependent ADNP mRNA distribution patterns, affected by aging. Future studies are aimed at deciphering the function of ADNP in birds, toward a better molecular understanding of sexual dichotomy in singing behavior in birds.
MeSH Terms
- Aging
- Animals
- Avian Proteins
- Female
- Gene Expression Regulation
- Male
- Mice
- Nerve Tissue Proteins
- RNA, Messenger
- Sex Characteristics
- Songbirds
- Vocalization, Animal
Keywords
- Activity-dependent neuroprotective protein (ADNP)
- Aging
- Sexual dimorphism
- Songbird brain
- Zebra finch
- qRT-PCR